MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Molecular Neurobiology' source. Wed, 08 Feb 2012 20:43:24 +0100 http://www.medworm.com/index.php?rid=5660919&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe35l63n53u822812%2F Abstract  Human brain cells rely on a specific subset of microRNAs (miRNAs or miRs) to shape their gene expression patterns, and this is mediated through microRNA effects on messenger RNA (mRNA) speciation and complexity. In recent studies (a) in short post-mortem interval Alzheimer’ disease (AD) brain tissues versus age-matched controls, and (b) in pro-inflammatory cytokine- and Aβ42 peptide-stressed human neuronal-glial (HNG) cells in primary culture, we have identified several brain-abundant miRNA species found to be significantly up-regulated, including miR-125b and miR-146a. Both of these nuclear factor kappa B (NF-κB)-activated, 22 nucleotide small non-coding RNAs (sncRNAs) target the mRNA of the key, innate-immune- and inflammation-related regulatory protein, com... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5660919 Thu, 02 Feb 2012 18:16:22 +0100 5660919 http://www.medworm.com/index.php?rid=5660920&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd3m68244343w3v1t%2F Abstract  Sortilin and SorLA are members of the Vps10p domain receptor family, the Sortilins, which comprise five type I transmembrane receptors differentially expressed in neuronal tissues of the central and peripheral nervous system. Since the identification of sortilin in 1997, members of this receptor family are recognized as sorting receptors primarily in the trans-Golgi network, interacting with a wide range of ligands comprising other transmembrane receptors as well as soluble proteins from neurotrophic factors to enzymes targeted for lysosomes. Specifically, the involvement of sortilin in neutrophin signaling in healthy and injured neurons is increasingly recognized, as well as the impact of SorLA on the cellular processing of amyloid precursor protein, an important... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5660920 Wed, 01 Feb 2012 17:12:04 +0100 5660920 http://www.medworm.com/index.php?rid=5639528&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqn573qr1181g57uu%2F Abstract  Genetic variation in clusterin gene, also known as apolipoprotein J, has been associated with Alzheimer’s disease (AD) through replicated genome-wide studies, and plasma clusterin levels are associated with brain atrophy, baseline prevalence and severity, and rapid clinical progression in patients with AD, highlighting the importance of clusterin in AD pathogenesis. Emerging data suggest that clusterin contributes to AD through various pathways, including amyloid-β aggregation and clearance, lipid metabolism, neuroinflammation, and neuronal cell cycle control and apoptosis. Moreover, epigenetic regulation of the clusterin expression also seems to play an important role in the pathogenesis of AD. Emerging knowledge of the contribution of clusterin to the pathoge... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5639528 Tue, 24 Jan 2012 18:14:43 +0100 5639528 http://www.medworm.com/index.php?rid=5639529&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fyvw10666v7264523%2F Abstract  The goal of this study was to evaluate if the immunohistochemical expression of alpha-3 neuronal nicotinic acetylcholine receptor subunit in sympathetic ganglia remains stable after brain death, determining the possible use of sympathetic thoracic ganglia from subjects after brain death as study group. The third left sympathetic ganglion was resected from patients divided in two groups: BD—organ donors after brain death and CON—patients submitted to sympathectomy for hyperhidrosis (control group). Immunohistochemical staining for alpha-3 neuronal nicotinic acetylcholine receptor subunit was performed; strong and weak expression areas were quantified in both groups. The BD group showed strong alpha-3 neuronal nicotinic acetylcholine receptor expression in 6.55%... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5639529 Tue, 24 Jan 2012 18:14:42 +0100 5639529 http://www.medworm.com/index.php?rid=5639530&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F08313m01x32t2150%2F Content Type Journal ArticleCategory ErratumPages 1-1DOI 10.1007/s12035-012-8238-0Authors Jia-Su Li, Department of Physiology, Squadron 4 of Cadet Brigade, Third Military Medical University, Chongqing, 400038 ChinaZhong-Xiang Yao, Department of Physiology, Third Military Medical University, Chongqing, 400038 China Journal Molecular NeurobiologyOnline ISSN 1559-1182Print ISSN 0893-7648 (Source: Molecular Neurobiology) Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5639530 Tue, 24 Jan 2012 07:21:06 +0100 5639530 http://www.medworm.com/index.php?rid=5621284&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx325543096152q64%2F Abstract  Classic theories suggest that central serotonergic neurons are involved in the behavioral inhibition that is associated with the prediction of negative rewards or punishment. Failed behavioral inhibition can cause impulsive behaviors. However, the behavioral inhibition that results from predicting punishment is not sufficient to explain some forms of impulsive behavior. In this article, we propose that the forebrain serotonergic system is involved in “waiting to avoid punishment” for future punishments and “waiting to obtain reward” for future rewards. Recently, we have found that serotonergic neurons increase their tonic firing rate when rats await food and water rewards and conditioned reinforcer tones. The rate of tonic firing during the delay period wa... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5621284 Fri, 20 Jan 2012 07:05:24 +0100 5621284 http://www.medworm.com/index.php?rid=5621285&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0245um902t470266%2F Abstract  Duchenne muscular dystrophy (DMD) causes cognitive impairment in one third of the patients, although the underlying mechanisms remain to be elucidated. Recent studies showed that mutations in the distal part of the dystrophin gene correlate well with the cognitive impairment in DMD patients, which is attributed to Dp71. The study on the expression of the shortest isoform, Dp40, has not been possible due to the lack of an isoform specific antibody. Dp40 has the same promoter as that found in Dp71 and lacks the normal C-terminal end of Dp427. In the present study, we have raised polyclonal antibody against the N-terminal sequence common to short isoforms of dystrophin, including Dp40, and investigated the expression pattern of Dp40 in the mouse brain. Affinity chrom... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5621285 Thu, 19 Jan 2012 06:57:32 +0100 5621285 http://www.medworm.com/index.php?rid=5573083&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff3u7g01574k1884j%2F Abstract  Although they are effective at treating the motor impairments that are the core symptoms of Parkinson’s disease, current treatments, namely l-3,4-dihydroxyphenylalanine (l-DOPA), the gold standard medication and high-frequency stimulation of the subthalamic nucleus (HFS-STN), can lead to cognitive and mood alterations. Many of these side effects, such as depression, anxiety and sleep disturbances, could be related to abnormal functioning of the serotonergic system, but much basic research remains to be done. Molecular studies in humans and animal models of the disease have reported diverse drastic changes to the serotonergic system. It has also been shown that the serotonergic system both plays a major role in the mechanism of action of the current therapies and ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5573083 Thu, 05 Jan 2012 17:04:58 +0100 5573083 http://www.medworm.com/index.php?rid=5573084&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7136277vk10u110p%2F Abstract  MicroRNAs (miRNAs or miRs) are a class of endogenous small non-coding RNAs that consist of about 22 nucleotides and play critical roles in various biological processes, including cell proliferation, differentiation, apoptosis, and tumorigenesis. In recent years, some specific miRNA, such as miR-219, miR-138, miR-9, miR-23, and miR-19b were found to participate in the regulation of oligodendrocyte (OL) differentiation and myelin maintenance, as well as in the pathogenesis of demyelination-related diseases (e.g., multiple sclerosis, ischemic stroke, and leukodystrophy). These miRNAs control their target mRNA or regulate the protein levels of some signaling pathways, and participate in OL differentiation and the pathogenesis of demyelination-related diseases. During ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5573084 Wed, 04 Jan 2012 16:59:46 +0100 5573084 http://www.medworm.com/index.php?rid=5553332&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv215440p00702441%2F Abstract  Alterations occur within distal neuronal compartments, including axons and synapses, during the course of neurodegenerative diseases such as Parkinson’s disease (PD). These changes could hold important implications for the functioning of neural networks, especially since research studies have shown a loss of dendritic spines locating to medium spiny projection neurons and impaired axonal transport in PD-affected brains. However, despite ever-increasing awareness of the vulnerability of synapses and axons, inadequate understanding of the independent mechanisms regulating non-somatic neurodegeneration prevails. This has resulted in limited therapeutic strategies capable of targeting these distinct cellular compartments. Deregulated protein synthesis, folding and d... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5553332 Wed, 28 Dec 2011 16:49:29 +0100 5553332 http://www.medworm.com/index.php?rid=5553333&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6421714272717522%2F Abstract  Insulin receptors in the brain are found in high densities in the hippocampus, a region that is fundamentally involved in the acquisition, consolidation, and recollection of new information. Using the intranasal method, which effectively bypasses the blood–brain barrier to deliver and target insulin directly from the nose to the brain, a series of experiments involving healthy humans has shown that increased central nervous system (CNS) insulin action enhances learning and memory processes associated with the hippocampus. Since Alzheimer's disease (AD) is linked to CNS insulin resistance, decreased expression of insulin and insulin receptor genes and attenuated permeation of blood-borne insulin across the blood–brain barrier, impaired brain insulin signaling c... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5553333 Wed, 28 Dec 2011 16:49:18 +0100 5553333 http://www.medworm.com/index.php?rid=5553334&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk0u2l9265wt770l8%2F Abstract  Huge progress has been made in unraveling the mysteries of Alzheimer’s disease (AD), but we still do not understand the basic mechanisms that set off the cascade of pathological events. In May 2011, the National Institute on Aging–Alzheimer’s Association published new diagnostic guidelines, expected to have huge impact on AD research and clinical practice. However, the new guidelines are already criticized for being biased in favor of a specific theory of the pathophysiological origins of AD—the amyloid cascade hypothesis. Shortly before publication of the guidelines, a hypothetical model of the dynamic biomarkers of the Alzheimer’s pathological cascade was published, taking as starting point that biomarkers reflecting brain levels of amyloid become devia... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5553334 Mon, 26 Dec 2011 16:45:30 +0100 5553334 http://www.medworm.com/index.php?rid=5545644&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff3026127m44521w8%2F This article presents an update on the usage and applications of melatonin in PD models along with incongruous observations. The impending implications in the clinics, success, limitations, and future prospective have also been discussed in this article. Content Type Journal ArticlePages 1-14DOI 10.1007/s12035-011-8225-xAuthors Naveen Kumar Singhal, Indian Institute of Toxicology Research (Council of Scientific and Industrial Research), Mahatma Gandhi Marg, Post Box 80, Lucknow, 226 001 UP, IndiaGarima Srivastava, Indian Institute of Toxicology Research (Council of Scientific and Industrial Research), Mahatma Gandhi Marg, Post Box 80, Lucknow, 226 001 UP, IndiaSonal Agrawal, Indian Institute of Toxicology Research (Council of Scientific and Industrial Research), Mahatma Gandhi Marg... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5545644 Fri, 23 Dec 2011 16:54:18 +0100 5545644 http://www.medworm.com/index.php?rid=5545645&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd5624r6446565333%2F Abstract  Spine morphogenesis and plasticity are intimately linked to cognition, and there is strong evidence that aberrant regulation of spine plasticity is associated with physiological, behavioral, and pathological conditions. The neuronal guanine nucleotide exchange factor (GEF) kalirin is emerging as a key regulator of structural and functional plasticity at dendritic spines. Here, we review recent studies that have genetically and functionally linked kalirin signaling to a number of human disorders. Kalirin signaling may thus represent a disease mechanism and provide a novel therapeutic target. Content Type Journal ArticlePages 1-10DOI 10.1007/s12035-011-8223-zAuthors Peter Penzes, Department of Physiology, Northwestern University Feinberg School of Medicine, 303... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5545645 Thu, 22 Dec 2011 12:51:16 +0100 5545645 http://www.medworm.com/index.php?rid=5527011&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2n648531p2641221%2F Abstract  The diverse activities of dopamine D2-like receptors, including D2, D3, and D4 receptors, are mediated by proteins that interact with the third cytoplasmic loop and regulate receptor signaling, receptor trafficking, and apoptosis. Such interacting proteins include calmodulin, the N-methyl-d-aspartate receptor 2B subunit, calcium/calmodulin-dependent protein kinase II, prostate apoptosis response-4, and β-arrestins, which regulate receptor signaling and the pharmacological action through D2 receptor. The gene encoding the D2 receptor gives rise to two isoforms, termed the dopamine D2 receptor long isoform (D2L) and the dopamine D2 receptor short isoform; the latter lacks 29 amino acids of the D2L receptor within the third cytoplasmic loop. In this review, we first ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5527011 Mon, 19 Dec 2011 16:52:47 +0100 5527011 http://www.medworm.com/index.php?rid=5516361&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7750000113781557%2F Abstract  Intracellular messenger RNA (mRNA) traffic and translation must be highly regulated, both temporally and spatially, within eukaryotic cells to support the complex functional partitioning. This capacity is essential in neurons because it provides a mechanism for rapid input-restricted activity-dependent protein synthesis in individual dendritic spines. While this feature is thought to be important for synaptic plasticity, the structures and mechanisms that support this capability are largely unknown. Certainly specialized RNA binding proteins and binding elements in the 3′ untranslated region (UTR) of translationally regulated mRNA are important, but the subtlety and complexity of this system suggests that an intermediate “specificity” component is also invol... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5516361 Tue, 13 Dec 2011 17:05:12 +0100 5516361 http://www.medworm.com/index.php?rid=5506826&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Frq7335p02n506pl8%2F Abstract  Cytokines encompass a broad class of peptides that mediate signals in a broad range of physiological situations including inflammation, infection, and obesity. The cytokine receptor-associated tyrosine kinase, Jak2, is one of the most important proteins mediating cytokine signaling pathway activation. Recently, our group has demonstrated that Jak2 signaling in the gonadotropin-releasing hormone (GnRH) neuron plays a critical role in fertility in males and females, implicating cytokine activation of the neuron in GnRH neuronal development and function. To date, the specific cytokine(s) essential for activating Jak2 during neuroendocrine development are not known. In this article, we review the evidence for the role of several class 1 cytokines in regulating GnRH ne... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5506826 Mon, 12 Dec 2011 17:12:27 +0100 5506826 http://www.medworm.com/index.php?rid=5495982&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6541701lg7v361r0%2F Abstract  There is much interest in the use of mesenchymal stem cells/marrow stromal cells (MSC) to treat neurodegenerative disorders, in particular those that are fatal and difficult to treat, such as Huntington’s disease. MSC present a promising tool for cell therapy and are currently being tested in FDA-approved phase I–III clinical trials for many disorders. In preclinical studies of neurodegenerative disorders, MSC have demonstrated efficacy, when used as delivery vehicles for neural growth factors. A number of investigators have examined the potential benefits of innate MSC-secreted trophic support and augmented growth factors to support injured neurons. These include overexpression of brain-derived neurotrophic factor and glial-derived neurotrophic factor, using ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5495982 Thu, 08 Dec 2011 18:25:05 +0100 5495982 http://www.medworm.com/index.php?rid=5478053&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb7105n6445187j56%2F Abstract  Organization of presynaptic active zones is essential for development, plasticity, and pathology of the nervous system. Recent studies indicate a trans-synaptic molecular mechanism that organizes the active zones by connecting the pre- and the postsynaptic specialization. The presynaptic component of this trans-synaptic mechanism is comprised of cytosolic active zone proteins bound to the cytosolic domains of voltage-dependent calcium channels (P/Q-, N-, and L-type) on the presynaptic membrane. The postsynaptic component of this mechanism is the synapse organizer (laminin β2) that is expressed by the postsynaptic cell and accumulates specifically on top of the postsynaptic specialization. The pre- and the postsynaptic components interact directly between the extr... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5478053 Thu, 01 Dec 2011 19:30:42 +0100 5478053 http://www.medworm.com/index.php?rid=5459594&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu7h587473145p3nk%2F Summary  The transforming growth factor-β (TGF-β) superfamily is a multifunctional, contextually acting family of cytokines that participate in the regulation of development, disease and tissue repair in the nervous system. The TGF-β family is composed of several members, including TGF-βs, bone morphogenetic proteins (BMPs) and activins. In this review, we discuss recent findings that suggest TGF-β function as important pleiotropic modulators of nociceptive processing both physiologically and under pathological painful conditions. The strategy of increasing TGF-β signaling by deleting “BMP and activin membrane-bound inhibitor” (BAMBI), a TGF-β pseudoreceptor, has demonstrated the inhibitory role of TGF-β signaling pathways in normal nociception and in inflammator... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5459594 Mon, 28 Nov 2011 16:50:38 +0100 5459594 http://www.medworm.com/index.php?rid=5450340&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe3878716571r235t%2F Abstract  Adenosine deaminases acting on RNA (ADARs) are the enzymes that are responsible for the A to I RNA editing process in mammals, which is an important mechanism that increases molecular diversity. A to I RNA editing consists of an enzymatic conversion of specific adenosine in pre-mRNA, leading to alteration of the properties of both the RNA itself and the translated protein. Currently, the importance of this phenomenon is increasingly recognized as it affects a diverse set of cellular pathways. ADAR function within the cell, especially in the neurons, is to diversify the features of a limited set of unique transcripts, mostly neurotransmitter receptors; however, a growing set of target is going to be discovered, increasing the importance of the RNA editing event in ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5450340 Wed, 23 Nov 2011 17:37:58 +0100 5450340 http://www.medworm.com/index.php?rid=5450341&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F92168gk326r36283%2F Abstract  Cell–cell and cell–matrix interactions are necessary for neuronal patterning and brain wiring during development. Matrix metalloproteinases (MMPs) are proteolytic enzymes capable of remodelling the pericellular environment and regulating signaling pathways through cleavage of a large degradome. MMPs have been suggested to affect cerebellar development, but the specific role of different MMPs in cerebellar morphogenesis remains unclear. Here, we report a role for MMP-3 in the histogenesis of the mouse cerebellar cortex. MMP-3 expression peaks during the second week of postnatal cerebellar development and is most prominently observed in Purkinje cells (PCs). In MMP-3 deficient (MMP-3−/−) mice, a protracted granule cell (GC) tangential migration and a delayed ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5450341 Tue, 22 Nov 2011 18:01:26 +0100 5450341 http://www.medworm.com/index.php?rid=5443029&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg3h51965142q1u03%2F Abstract  Dystrophin Dp71 is expressed in all tissues, with the exception of skeletal muscle, and is the main Duchenne muscular dystrophy (DMD) gene product in brain. As full-length dystrophin does in skeletal muscle, Dp71 associates with dystroglycans, sarcoglycans, dystrobrevins, syntrophins, and accessory proteins to form the dystrophin-associated protein complex (DAPC) in non-muscle tissues. Although it has been nearly 20 years since the discovery of Dp71, its study has become relevant only recently due to its direct involvement with the two main DMD non-muscular phenotypes: cognitive impairment and abnormal retinal physiology. In this review, we describe the historical background of Dp71 and the experimental models developed for its study. Additionally, we present... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5443029 Mon, 21 Nov 2011 18:08:51 +0100 5443029 http://www.medworm.com/index.php?rid=5410499&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1v188l8727000k45%2F Abstract  Higher-order executive tasks such as learning, working memory, and behavioral flexibility depend on the prefrontal cortex (PFC), the brain region most elaborated in primates. The prominent innervation by serotonin neurons and the dense expression of serotonergic receptors in the PFC suggest that serotonin is a major modulator of its function. The most abundant serotonin receptors in the PFC, 5-HT1A, 5-HT2A and 5-HT3A receptors, are selectively expressed in distinct populations of pyramidal neurons and inhibitory interneurons, and play a critical role in modulating cortical activity and neural oscillations (brain waves). Serotonergic signaling is altered in many psychiatric disorders such as schizophrenia and depression, where parallel changes in receptor expressio... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5410499 Thu, 10 Nov 2011 16:56:07 +0100 5410499 http://www.medworm.com/index.php?rid=5410500&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4432385131vr7530%2F Abstract  Amyotrophic lateral sclerosis (ALS) is the third most common adult-onset neurodegenerative disease. It causes the degeneration of motoneurons and is fatal due to paralysis, particularly of respiratory muscles. ALS can be inherited, and specific disease-causing genes have been identified, but the mechanisms causing motoneuron death in ALS are not understood. No effective treatments exist for ALS. One well-studied theory of ALS pathogenesis involves faulty RNA editing and abnormal activation of specific glutamate receptors as well as failure of glutamate transport resulting in glutamate excitotoxicity; however, the excitotoxicity theory is challenged by the inability of anti-glutamate drugs to have major disease-modifying effects clinically. Nevertheless, hyperexcit... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5410500 Wed, 09 Nov 2011 17:56:36 +0100 5410500 http://www.medworm.com/index.php?rid=5365487&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F82xl1433kj34w343%2F Abstract  During brain development, each neuron must find and synapse with the correct pre- and postsynaptic partners. The complexity of these connections and the relatively large distances some neurons must send their axons to find the correct partners makes studying brain development one of the most challenging, and yet fascinating disciplines in biology. Furthermore, once the initial connections have been made, the neurons constantly remodel their dendritic and axonal arbours in response to changing demands. Neurexin and neuroligin are two cell adhesion molecules identified as important regulators of this process. The importance of these genes in the development and modulation of synaptic connectivity is emphasised by the observation that mutations in these genes in huma... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5365487 Sun, 30 Oct 2011 05:37:33 +0100 5365487 http://www.medworm.com/index.php?rid=5338233&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe44114187851056p%2F Abstract  The prevalence of obesity and its associated medical complications, including type 2 diabetes and cardiovascular disease, continues to rise globally. Lifestyle changes in the last decades have greatly contributed to the current obesity trends. However, inheritable biological factors that disrupt the tightly regulated equilibrium between caloric intake and energy expenditure also appear to play a critical part. Mounting evidence obtained from human and rodent studies suggests that perturbed brain-derived neurotrophic factor (BDNF) signaling in appetite-regulating centers in the brain might be a culprit. Here, we review findings that inform the critical roles of BDNF and its receptor TrkB in energy balance and reward centers of the brain impacting feeding behavior a... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5338233 Wed, 19 Oct 2011 15:51:34 +0100 5338233 http://www.medworm.com/index.php?rid=5316910&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7448231231778843%2F Abstract  Mood disorders, such as bipolar and major depressive disorders, are frequent, severe, and often disabling neuropsychiatric diseases affecting millions of individuals worldwide. Available mood stabilizers and antidepressants remain unsatisfactory because of their delayed and partial therapeutic efficacy. Therefore, the development of targeted therapies, working more rapidly and being fully effective, is urgently needed. In this context, the protein kinase C (PKC) signaling system, which regulates multiple neuronal processes implicated in mood regulation, can constitute a novel therapeutic target. This paper reviews the currently available knowledge regarding the role of the PKC signaling pathway in the pathophysiology of mood disorders and the therapeutic potential... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5316910 Sat, 08 Oct 2011 05:51:03 +0100 5316910 http://www.medworm.com/index.php?rid=5298212&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd51202j655pm5853%2F Abstract  The development of the central nervous system (CNS) relies on precisely orchestrated gene expression regulation. Dysregulation of both genetic and environmental factors can affect proper CNS development and results in neurological diseases. Recent studies have shown that similar to protein coding genes, noncoding RNA molecules have a significant impact on normal CNS development and on causes and progression of human neurological disorders. In this review, we have highlighted discoveries of functions of noncoding RNAs, in particular microRNAs and long noncoding RNAs, in neural development and neurological diseases. Emerging evidence has shown that microRNAs play an essential role in many aspects of neural development, such as proliferation of neural stem cells and ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5298212 Tue, 04 Oct 2011 05:51:05 +0100 5298212 http://www.medworm.com/index.php?rid=5287518&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F05m64n73r8355460%2F Abstract  Adult neurogenesis is a unique form of plasticity found in the hippocampus, a brain region key to learning and memory formation. While many external stimuli are known to modulate the generation of new neurons in the hippocampus, little is known about the local circuitry mechanisms that regulate the process of adult neurogenesis. The neurogenic niche in the hippocampus is highly complex and consists of a heterogeneous population of cells including interneurons. Because interneurons are already highly integrated into the hippocampal circuitry, they are in a prime position to influence the proliferation, survival, and maturation of adult-generated cells in the dentate gyrus. Here, we review the current state of our understanding on the interplay between interneurons ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5287518 Thu, 29 Sep 2011 06:15:51 +0100 5287518 http://www.medworm.com/index.php?rid=5252130&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1qr85860t6m135m6%2F We describe a mechanism whereby chronic blockade of opiate receptors, in spite of only partial opiate agonist action, may ultimately block dopaminergic activity causing anti-reward and relapse potential. While the direct comparison is not as yet available, toxicity to buprenorphine can be found in the scientific literature. In considering our cautionary note in this commentary, we are cognizant that, to date, this is what we have available, and until such a time when the real magic bullet is discovered, we will have to endure. However, more than anything else this commentary should at least encourage the development of thoughtful new strategies to target the specific brain regions responsible for relapse prevention. Content Type Journal ArticlePages 1-19DOI 10.1007/s12035-011-82... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5252130 Fri, 23 Sep 2011 15:50:37 +0100 5252130 http://www.medworm.com/index.php?rid=5252131&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm56064ww33476288%2F Abstract  In neurons, the convergence of multiple intracellular signaling cascades leading to cAMP-responsive element-binding protein (CREB) activation suggests that this transcription factor plays a critical role in integrating different inputs and mediating appropriate neuronal responses. The nature of this transcriptional response depends on both the type and strength of the stimulus and the cellular context. CREB-dependent gene expression has been involved in many different aspects of nervous system function, from embryonic development to neuronal survival, and synaptic, structural, and intrinsic plasticity. Here, we first review the different methodological approaches used to genetically manipulate CREB activity and levels in neurons in vivo in the adult brain, includi... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5252131 Fri, 23 Sep 2011 05:46:23 +0100 5252131 http://www.medworm.com/index.php?rid=5252132&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj64p511578124102%2F Abstract  Acidosis is a common feature of many neuronal diseases and often accompanied with adverse consequences such as pain and neuronal injury. Before the discovery of acid-sensing ion channels (ASICs), protons were usually considered as a modulator of other ion channels, such as voltage-gated calcium channels, N-methyl-d-aspartate, and γ-amino butyric acid(A) receptor channels. Accordingly, the functional effects of acidosis were considered as consequences of modulations of these channels. Since the first cloning of ASICs in 1997, the conventional view on acidosis-mediated pain and cell injury has been dramatically changed. To date, ASICs, which are directly activated by extracellular protons, are shown to mediate most of the acidosis-associated physiological and pathol... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5252132 Tue, 20 Sep 2011 05:49:38 +0100 5252132 http://www.medworm.com/index.php?rid=5240036&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp78j20443w10632n%2F Abstract  The importance of phosphoinositides (phosphorylated phosphatidyl inositol derivatives, PIs) for normal cellular function cannot be overstated. Although they represent a small fraction of the total phospholipid within the cell, they are essential regulators of many cellular functions. They direct membrane trafficking by functioning as recruitment factors for vesicular trafficking components, they can modulate ion channel activity through direct binding within cellular membranes, and their hydrolysis generates second messenger signaling molecules. Despite an explosion of information regarding the importance of these lipids in cellular biology, their precise roles in vertebrate retinal photoreceptors has not been established. This review summarizes the literature on ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5240036 Sat, 17 Sep 2011 16:55:00 +0100 5240036 http://www.medworm.com/index.php?rid=5228152&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F162j01040122hg57%2F Abstract  Drug addiction is a chronic neuronal disease. In recent years, proteomics technology has been widely used to assess the protein expression in the brain tissues of both animals and humans exposed to addictive drugs. Through this approach, a large number of proteins potentially involved in the etiology of drug addictions have been identified, which provide a valuable resource to study protein function, biochemical pathways, and networks related to the molecular mechanisms underlying drug dependence. In this article, we summarize the recent application of proteomics to profiling protein expression patterns in animal or human brain tissues after the administration of alcohol, amphetamine/methamphetamine, cocaine, marijuana, morphine/heroin/butorphanol, or nicotine. Fr... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5228152 Fri, 16 Sep 2011 05:50:15 +0100 5228152 http://www.medworm.com/index.php?rid=5228153&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj2w4403l7h5551v5%2F Abstract  All sensory receptors adapt. As the mean level of light or sound or odor is altered, the sensitivity of the receptor is adjusted to permit the cell to function over as wide a range of ambient stimulation as possible. In a rod photoreceptor, adaptation to maintained background light produces a decrease (or “sag”) in the response to the prolonged illumination, as well as an acceleration in response decay time and a Weber–Fechner-like decrease in sensitivity. Earlier work on salamander indicated that adaptation is controlled by the intracellular concentration of Ca2+. Three Ca2+-dependent mechanisms were subsequently identified, namely, regulation of guanylyl cyclase, modulation of activated rhodopsin lifetime, and alteration of channel opening probability, with... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5228153 Thu, 15 Sep 2011 15:47:52 +0100 5228153 http://www.medworm.com/index.php?rid=5228154&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv068372515650744%2F Abstract  The harmony and function of the complex brain circuits and synapses are sustained mainly by excitatory and inhibitory neurotransmission, neurotrophins, gene regulation, and factors, many of which are incompletely understood. A common feature of brain circuit components, such as dendrites, synaptic membranes, and other membranes of the nervous system, is that they are richly endowed in docosahexaenoic acid (DHA), the main member of the omega-3 essential fatty acid family. DHA is avidly retained and concentrated in the nervous system and known to play a role in neuroprotection, memory, and vision. Only recently has it become apparent why the surprisingly rapid increases in free (unesterified) DHA pool size take place at the onset of seizures or brain injury. This ph... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5228154 Wed, 14 Sep 2011 16:09:06 +0100 5228154 http://www.medworm.com/index.php?rid=5211285&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8ul766278802p601%2F Abstract  A key requirement for encoding the auditory environment is the ability to dynamically alter cochlear sensitivity. However, merely attaining a steady state of maximal sensitivity is not a viable solution since the sensory cells and ganglion cells of the cochlea are prone to damage following exposure to loud sound. Most often, such damage is via initial metabolic insult that can lead to cellular death. Thus, establishing the highest sensitivity must be balanced with protection against cellular metabolic damage that can lead to loss of hair cells and ganglion cells, resulting in loss of frequency representation. While feedback mechanisms are known to exist in the cochlea that alter sensitivity, they respond only after stimulus encoding, allowing potentially damaging ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5211285 Sat, 10 Sep 2011 15:48:34 +0100 5211285 http://www.medworm.com/index.php?rid=5211286&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F14t2644w63l71552%2F Abstract  The Flamingo/Celsr seven-transmembrane cadherins represent a conserved subgroup of the cadherin superfamily involved in multiple aspects of development. In the developing nervous system, Fmi/Celsr control axonal blueprint and dendritic morphogenesis from invertebrates to mammals. As expected from their molecular structure, seven-transmembrane cadherins can induce cell–cell homophilic interactions but also intracellular signaling. Fmi/Celsr is known to regulate planar cell polarity (PCP) through interactions with PCP proteins. In the nervous system, Fmi/Celsr can function in collaboration with or independently of other PCP genes. Here, we focus on recent studies which show that seven-transmembrane cadherins use distinct molecular mechanisms to achieve diverse fun... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5211286 Sat, 10 Sep 2011 06:01:39 +0100 5211286 http://www.medworm.com/index.php?rid=5164455&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx2gg70j656870407%2F Abstract  Myelinated axons are a beautiful example of symbiotic interactions between two cell types: Myelinating glial cells organize axonal membranes and build their myelin sheaths to allow fast action potential conduction, while axons regulate myelination and enhance the survival of myelinating cells. Axonal demyelination, occurring in neurodegenerative diseases or after a nerve injury, results in severe motor and/or mental disabilities. Thus, understanding how the myelination process is induced, regulated, and maintained is crucial to develop new therapeutic strategies for regeneration in the nervous system. Epigenetic regulation has recently been recognized as a fundamental contributing player. In this review, we focus on the central mechanisms of gene regulation mediat... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5164455 Mon, 22 Aug 2011 15:59:08 +0100 5164455 http://www.medworm.com/index.php?rid=5164454&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff025652425661384%2F Abstract  Neural circuits associated with retinal ganglion cells have long been used as models for investigating the mechanisms that govern circuit development and function. Similar to neurons in the brain, retinal ganglion cells are subdivided into distinct classes based upon their morphology, physiology, and patterns of connectivity. Newly developed transgenic tools in which individual classes of retinal ganglion cells are labeled with reporter proteins have recently provided a method to study the development of their class-specific circuitry. Here, we examine a single class of intrinsically photosensitive retinal ganglion cells and discuss their class-specific circuitry, as well as the cellular and molecular mechanisms that govern assembly of this circuitry. Content... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5164454 Mon, 22 Aug 2011 15:59:08 +0100 5164454 http://www.medworm.com/index.php?rid=5022605&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F200076v00025ku68%2F Abstract  MicroRNAs (miRNAs, miRs) are small, non-coding RNA molecules that regulate gene expression posttranscriptionally. Although discovered only recently in the early 1990s, this relatively new group of molecules has already been proven to play an essential role in the regulation of many physiological and, most importantly, pathological processes such as cancer. A large number of miRNAs has been found to be involved in the pathogenesis of various human malignancies, and expression of miRNAs has been demonstrated to correlate with clinic and outcome. In tumors of the brain, however, the investigations on the role of miRNAs are still in its infancy, and most publications refer to the most common primary brain tumor, the glioma (mostly glioblastoma). But despite the fact t... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5022605 Fri, 08 Jul 2011 06:31:56 +0100 5022605 http://www.medworm.com/index.php?rid=5001289&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6005577228u507q1%2F Abstract  MicroRNAs are endogenous non-coding small RNAs that have been described as highly conserved regulators of gene expression. They are involved in cancer and in the regulation of neural development and stem cell function. Recent studies suggest that a small subpopulation of cancer stem cells (CSCs) has the capacity to repopulate solid tumours such as glioblastoma (GBM), drive malignant progression and mediate radio- and chemoresistance. GBM-derived CSCs share the fundamental stem cell properties of self-renewal and multipotency with neural stem cells (NSCs) and may be regulated by miRNAs. In this review, we will summarize the current knowledge regarding the role of miRNAs in GBM development with a focus on the regulation of GBM-CSCs. We propose a list of miRNAs that ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=5001289 Mon, 04 Jul 2011 16:19:49 +0100 5001289 http://www.medworm.com/index.php?rid=4994579&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F530877414706538q%2F Abstract  Although the incidence of HIV-associated dementia (HAD) has declined, HIV-associated neurocognitive disorders (HAND) remain a significant health problem despite use of highly active antiretroviral therapy. In addition, the incidence and/or severity of HAND/HAD are increased with concomitant use of drugs of abuse, such as cocaine, marijuana, and methamphetamine. Furthermore, exposure to most drugs of abuse increases brain levels of dopamine, which has been implicated in the pathogenesis of HIV. This review evaluates the potential role of dopamine in the potentiation of HAND/HAD by drugs of abuse. In the brain, multiplication of HIV in infected macrophages/microglia could result in the release of HIV proteins such as gp120 and Tat, which can bind to and impair dopam... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4994579 Thu, 30 Jun 2011 06:08:41 +0100 4994579 http://www.medworm.com/index.php?rid=4978725&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc10445v533482187%2F Abstract  The potassium channel tetramerization domain-containing protein 7 (KCTD7) was named after the structural homology of its predicted N-terminal broad complex, tramtrack and bric à brac/poxvirus and zinc finger domain with the T1 domain of the Kv potassium channel, but its expression profile and cellular function are still largely unknown. We have recently reported a homozygous nonsense mutation of KCTD7 in patients with a novel form of autosomal recessive progressive myoclonic epilepsy. Here, we show that KCTD7 expression hyperpolarizes the cell membrane and reduces the excitability of transfected neurons in patch clamp experiments. We found the expression of KCTD7 in the hippocampal and Purkinje cells of the murine brain, an expression profile consistent with our ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4978725 Mon, 27 Jun 2011 17:50:26 +0100 4978725 http://www.medworm.com/index.php?rid=4971630&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg3287j041r078358%2F Abstract  Autism spectrum disorder (ASD) is a severe, complex neurodevelopmental disorder characterized by impairments in reciprocal social interaction and communication, and restricted and stereotyped patterns of interests and behaviors. Recent evidence has unveiled an important role for calcium (Ca2+) signaling in the pathogenesis of ASD. Post-mortem studies of autistic brains have pointed toward abnormalities in mitochondrial function as possible downstream consequences of altered Ca2+ signaling, abnormal synapse formation, and dysreactive immunity. SLC25A12, an ASD susceptibility gene, encodes the Ca2+-regulated mitochondrial aspartate–glutamate carrier, isoform 1 (AGC1). AGC1 is an important component of the malate/aspartate shuttle, a crucial system supporting oxidati... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4971630 Tue, 21 Jun 2011 16:41:39 +0100 4971630 http://www.medworm.com/index.php?rid=4971631&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F016l016607833755%2F Content Type Journal ArticlePages 1-1DOI 10.1007/s12035-011-8191-3Authors Rao S. Rapaka, National Institute on Drug Abuse, National Institutes of Health, 6001 Executive Blvd, Bethesda, MD 20892, USAPaul Schnur, National Institute on Drug Abuse, National Institutes of Health, 6001 Executive Blvd, Bethesda, MD 20892, USADavid Shurtleff, National Institute on Drug Abuse, National Institutes of Health, 6001 Executive Blvd, Bethesda, MD 20892, USA Journal Molecular NeurobiologyOnline ISSN 1559-1182Print ISSN 0893-7648 (Source: Molecular Neurobiology) Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4971631 Tue, 21 Jun 2011 16:41:37 +0100 4971631 http://www.medworm.com/index.php?rid=4947447&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx253726t214688r3%2F Abstract  Tauopathies are a group of neurodegenerative disorders characterised by altered levels of phosphorylation or mutations in the neuronal microtubule protein Tau. The heterogeneous pathology of tauopathies suggests differential susceptibility of different neuronal types to wild-type and mutant Tau. The genetic power and facility of the Drosophila model has been instrumental in exploring the molecular aetiologies of tauopathies, identifying additional proteins likely contributing to neuronal dysfunction and toxicity and novel Tau phosphorylations mediating them. Importantly, recent results indicate tissue- and temporal-specific effects on dysfunction and toxicity coupled with differential effects of distinct Tau isoforms within them. Therefore, they reveal an unexpecte... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4947447 Fri, 17 Jun 2011 10:56:15 +0100 4947447 http://www.medworm.com/index.php?rid=4896812&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F63620u2458862028%2F Abstract  Acetyl-l-carnitine (ALC), the acetyl ester of l-carnitine, is a naturally occurring molecule which plays an essential role in intermediary and mitochondrial metabolism. It has also neurotrophic and antioxidant actions, demonstrating efficacy and high tolerability in the treatment of neuropathies of various etiologies. ALC is a molecule of considerable interest for its clinical application in various neural disorders, although little is known regarding its effects on gene expression. Suppression subtractive hybridization methodology was used for the generation of subtracted complementary DNA libraries and the subsequent identification of differentially expressed transcripts in the rat brain after chronic ALC treatments. We provided evidence for a downregulation of t... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4896812 Wed, 25 May 2011 15:58:20 +0100 4896812 http://www.medworm.com/index.php?rid=4896813&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv0212142116wq132%2F Abstract  Conventional long-term potentiation (LTP) and long-term depression (LTD) are induced by different patterns of synaptic stimulation, but both forms of synaptic modification require calcium influx through NMDA receptors (NMDARs). A prevailing model (the “calcium hypothesis”) suggests that high postsynaptic calcium elevation results in LTP, whereas moderate elevations give rise to LTD. Recently, additional evidence has come to suggest that differential activation of NMDAR subunits also factors in determining which type of plasticity is induced. While the growing amount of data suggest that activation of NMDARs containing specific GluN2 subunits plays an important role in the induction of plasticity, it remains less clear which subunit is tied to which form of pla... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4896813 Sat, 21 May 2011 23:06:57 +0100 4896813 http://www.medworm.com/index.php?rid=4823371&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm102872767464322%2F Abstract  Excitatory transmission within hippocampal area CA3 stems from three major glutamatergic pathways: the perforant path formed by axons of layer II stellate cells in the entorhinal cortex, the mossy fiber axons originating from the dentate gyrus granule cells, and the recurrent axon collaterals of CA3 pyramidal cells. The synaptic communication of each of these pathways is modulated by metabotropic glutamate receptors that fine-tune the signal by affecting both the timing and strength of the connection. Within area CA3 of the hippocampus, group I mGluRs (mGluR1 and mGluR5) are expressed postsynaptically, whereas group II (mGluR2 and mGluR3) and III mGluRs (mGluR4, mGluR7, and mGluR8) are expressed presynaptically. Receptors from each group have been demonstrated to ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4823371 Wed, 11 May 2011 05:50:23 +0100 4823371 http://www.medworm.com/index.php?rid=4823370&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw83740825l751u35%2F Content Type Journal ArticlePages 1-1DOI 10.1007/s12035-011-8188-yAuthors Giovanni Scapagnini, Department of Health Sciences, University of Molise, Campobasso, ItalySonya Vasto, Immunosenescence Unit, Department of Pathobiology and Biomedical Methodologies, University of Palermo, Palermo, ItalyNader G. Abraham, Department of Physiology and Pharmacology, College of Medicine, University of Toledo, Toledo, OH, USACalogero Caruso, Immunosenescence Unit, Department of Pathobiology and Biomedical Methodologies, University of Palermo, Palermo, ItalyDavide Zella, Department of Biochemistry and Molecular Biology, Institute of Human Virology-School of Medicine, University of Maryland, Baltimore, MD, USAFabio Galvano, Department of Drug Science, University of Catania, Catania, Italy Journa... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4823370 Wed, 11 May 2011 05:50:23 +0100 4823370 http://www.medworm.com/index.php?rid=4807704&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp6p8n0807822231q%2F Abstract  Immunophilins are a family of highly conserved proteins with a peptidyl-prolyl isomerase activity that binds immunosuppressive drugs such as FK506, cyclosporin A, and rapamycin. Immunophilins can be divided into two subfamilies, the cyclophilins, and the FK506 binding proteins (FKBPs). Next to the immunophilins, a third group of peptidyl-prolyl isomerases exist, the parvulins, which do not influence the immune system. The beneficial role of immunophilin ligands in neurodegenerative disease models has been known for more than a decade but remains largely unexplained in terms of molecular mechanisms. In this review, we summarize reported effects of parvulins, immunophilins, and their ligands in the context of neurodegeneration. We focus on the role of FKBP12 in Park... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4807704 Fri, 06 May 2011 16:20:25 +0100 4807704 http://www.medworm.com/index.php?rid=4807705&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj174775036138161%2F Abstract  It is a common and widely accepted assumption that glycine and GABA are the main inhibitory transmitters in the central nervous system (CNS). But, in the past 20 years, several studies have clearly demonstrated that these amino acids can also be excitatory in the immature central nervous system. In addition, it is now established that both GABA receptors (GABARs) and glycine receptors (GlyRs) can be located extrasynaptically and can be activated by paracrine release of endogenous agonists, such as GABA, glycine, and taurine. Recently, non-synaptic release of GABA, glycine, and taurine gained further attention with increasing evidence suggesting a developmental role of these neurotransmitters in neuronal network formation before and during synaptogenesis. This... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4807705 Thu, 05 May 2011 16:36:09 +0100 4807705 http://www.medworm.com/index.php?rid=4791268&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0x46v80416j13676%2F Abstract  Neurogenesis occurs throughout adulthood in the mammalian brain. Newly born neurons are incorporated into the functional networks of both the olfactory bulb and the hippocampal dentate gyrus, and there is growing evidence that adult neurogenesis is important for various brain functions. Continuous neurogenesis is achieved by the coordinated proliferation and differentiation of adult neural stem cells. In this review, we discuss the recent findings concerning the roles of Notch signaling in adult neural stem cells. Content Type Journal ArticlePages 1-6DOI 10.1007/s12035-011-8186-0Authors Itaru Imayoshi, Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Sakyo-ku, Kyoto, 606-8507 JapanRyoichiro Kageyama, Institute for Virus Research, Kyoto Univer... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4791268 Tue, 03 May 2011 19:48:55 +0100 4791268 http://www.medworm.com/index.php?rid=4784139&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy4l5423441545611%2F Abstract  The Hsp90-associated cis-trans peptidyl-prolyl isomerase—FK506 binding protein 51 (FKBP51)—was recently found to co-localize with the microtubule (MT)-associated protein tau in neurons and physically interact with tau in brain tissues from humans who died from Alzheimer’s disease (AD). Tau pathologically aggregates in neurons, a process that is closely linked with cognitive deficits in AD. Tau typically functions to stabilize and bundle MTs. Cellular events like calcium influx destabilize MTs, disengaging tau. This excess tau should be degraded, but sometimes it is stabilized and forms higher-order aggregates, a pathogenic hallmark of tauopathies. FKBP51 was also found to increase in forebrain neurons with age, further supporting a novel role for FKBP51 in ta... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4784139 Wed, 27 Apr 2011 07:40:53 +0100 4784139 http://www.medworm.com/index.php?rid=4769029&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fdw82468238l5wt52%2F Abstract  There is growing interest in the biology of dysbindin and its genetic locus (DTNBP1) due to genetic variants associated with an increased risk of schizophrenia. Reduced levels of dysbindin mRNA and protein in the hippocampal formation of schizophrenia patients further support involvement of this locus in disease risk. Here, we discuss phylogenetically conserved dysbindin molecular interactions that define its contribution to the assembly of the biogenesis of lysosome-related organelles complex-1 (BLOC-1). We explore fundamental cellular processes where dysbindin and the dysbindin-containing BLOC-1 complex are implicated. We propose that cellular, tissue, and system neurological phenotypes from dysbindin deficiencies in model genetic organisms, and likely individual... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4769029 Mon, 25 Apr 2011 16:38:47 +0100 4769029 http://www.medworm.com/index.php?rid=4745413&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9142528l36368001%2F Abstract  There is increasing evidence that the same brain reward circuits involved in perpetuating drug abuse are involved in the hedonic urges and food cravings observed clinically in overweight and obese subjects. A polymorphism of the D2 dopamine receptor which renders it less sensitive to dopamine stimulation has been proposed to promote self-stimulatory behavior such as consuming alcohol, abusing drugs, or binging on foods. It is important to determine how this polymorphism may interact with other well-known candidate genes for obesity including polymorphisms of the leptin receptor gene and the opiomelanocortin gene. Leptin is a proinflammatory cytokine as well as a long-term signal maintaining body fat. Upper-body obesity stimulates systemic inflammation through the ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4745413 Mon, 18 Apr 2011 05:33:52 +0100 4745413 http://www.medworm.com/index.php?rid=4745414&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0645322vr324lj43%2F Abstract  In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies, for the beneficial effects of some phenolic substances, contained in commonly used spices and herbs, in preventing various age-related pathologic conditions, ranging from cancer to neurodegenerative diseases. Although the exact mechanisms by which polyphenols promote these effects remain to be elucidated, several reports have shown their ability to stimulate a general xenobiotic response in the target cells, activating multiple defense genes. Data from our and other laboratories have previously demonstrated that curcumin, the yellow pigment of curry, strongly induces heme-oxygenase-1 (HO-1) expression and activity in different brain cells vi... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4745414 Mon, 18 Apr 2011 05:33:51 +0100 4745414 http://www.medworm.com/index.php?rid=4660186&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd0v2574254086j04%2F Abstract  Mimicking the natural brain environment during neurogenesis represents the main challenge for efficient in vitro neuronal differentiation of stem cells. The discovery of miRNAs opens new possibilities in terms of modulation of stem cells lineage commitment and differentiation. Many studies demonstrated that in vitro transient overexpression or inhibition of brain-specific miRNAs in stem cells significantly directed differentiation along neuronal cell lineages. Modulating miRNA expression offers new pathways for post-transcriptional gene regulation and stem cell commitment. Neurotrophins and neuropoietins signaling pathways are the main field of investigation for neuronal commitment, differentiation, and maturation. This review will highlight examples of crosstalk ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4660186 Tue, 29 Mar 2011 06:09:16 +0100 4660186 http://www.medworm.com/index.php?rid=4628354&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2503k724573u272r%2F Abstract  An increasing number of studies have evaluated the potential therapeutic relevance of histone deacetylases (HDAC) inhibitors in mood disorder including bipolar disorder (BD). It has been suggested that the anterior limbic, which controls impulsivity and psychosis, is dysfunctional in BD. The present studies aims to evaluate the effects of microinjection of HDAC inhibitors in the ventricle, amygdala, striatum, prefrontal, and hippocampus on m-amphetamine-induced manic-like behavior in rats. Rats were given a single intracerebral (in the ventricle, amygdala, striatum, prefrontal, or hippocampus) injection of artificial cerebrospinal fluid, sodium butyrate (SB), or valproate (VPA) followed by an intraperitoneal injection of saline or m-AMPH 2 h before the open-f... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4628354 Mon, 21 Mar 2011 18:56:51 +0100 4628354 http://www.medworm.com/index.php?rid=4628355&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr36k788573736188%2F In conclusion, we highlight GPCR dimerization and G protein-independent signaling as two promising future directions in 5-HT7 receptor research, which ultimately might lead to the development of more efficient dimer- and/or pathway-specific therapeutics. Content Type Journal ArticlePages 1-26DOI 10.1007/s12035-011-8175-3Authors Anne Matthys, Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Department of Physiology, Ghent University (UGent), K.L. Ledeganckstraat 35, 9000 Ghent, BelgiumGuy Haegeman, Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Department of Physiology, Ghent University (UGent), K.L. Ledeganckstraat 35, 9000 Ghent, BelgiumKathleen Van Craenenbroeck, Laboratory of Eukaryotic Gene Expression and Signal Transductio... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4628355 Mon, 21 Mar 2011 18:56:50 +0100 4628355 http://www.medworm.com/index.php?rid=4628356&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh84k14p5383j376x%2F We present the argument that the AD research field requires more multifaceted analyses into the impacts of Alzheimer’s pathogenesis which combine simultaneous molecular-, circuit-, and behavior-level approaches. Supporting this argument is a review of particular research utilizing similar, “systems-level” methods in mouse models of AD. Related to this, a critique of common physiological and behavioral models is made—highlighting the likely usefulness of more refined and specific tools in understanding the relationship between candidate molecular pathologies and behavioral dysfunction. Finally, we propose challenges for future research which, if met, may greatly extend our current understanding of how AD molecular pathology impacts neural network function and behavior and poss... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4628356 Mon, 21 Mar 2011 18:56:49 +0100 4628356 http://www.medworm.com/index.php?rid=4607504&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv53uu1361wv32033%2F Content Type Journal ArticlePages 1-3DOI 10.1007/s12035-011-8173-5Authors Rita Levi-Montalcini, European Brain Research Institute, Rome, ItalyRichard A. Knight, Medical Research Council Toxicology Unit, Leicester, UKPierluigi Nicotera, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, GermanyGiuseppe Nisticó, European Brain Research Institute, Rome, ItalyNicolas Bazan, LSU Neuroscience Center of Excellence, New Orleans, LA USAGerry Melino, European Brain Research Institute, Rome, Italy Journal Molecular NeurobiologyOnline ISSN 1559-1182Print ISSN 0893-7648 (Source: Molecular Neurobiology) Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4607504 Tue, 15 Mar 2011 05:49:19 +0100 4607504 http://www.medworm.com/index.php?rid=4578811&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2xw01575985447g2%2F Abstract  Supplemental creatine has been promoted for its positive health effects and is best known for its use by athletes to increase muscle mass. In addition to its role in physical performance, creatine supplementation has protective effects on the brain in models of neuronal damage and also alters mood state and cognitive performance. Creatine is found in high protein foods, such as fish or meat, and is also produced endogenously from the biosynthesis of arginine, glycine, and methionine. Changes in brain creatine levels, as measured using magnetic resonance spectroscopy, are seen in individuals exposed to drugs of abuse and depressed individuals. These changes in brain creatine indicate that energy metabolism differs in these populations relative to healthy individual... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4578811 Fri, 11 Mar 2011 18:05:32 +0100 4578811 http://www.medworm.com/index.php?rid=4578812&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk653151012mn7969%2F In conclusion, NPD1 exhibits anti-inflammatory, anti-amyloidogenic, and anti-apoptotic bioactivities in human neural cells in part via PPARγ signaling and through the targeting of α- and β-secretase systems. Content Type Journal ArticlePages 1-8DOI 10.1007/s12035-011-8174-4Authors David T. Stark, Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite D, New Orleans, LA 70112, USANicolas G. Bazan, Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite D, New Orleans, LA 70112, USA Journal Molecular NeurobiologyOnline ISSN 1559-1182Print ISSN 0893-7648 (Source: Molecular Neurobiology) Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4578812 Wed, 09 Mar 2011 16:52:39 +0100 4578812 http://www.medworm.com/index.php?rid=4567556&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp771k0n361j73467%2F Abstract  p73, a transcription factor of the p53 family, plays a key role in many biological processes including neuronal development. Indeed, mice deficient for both TAp73 and ΔNp73 isoforms display neuronal pathologies, including hydrocephalus and hippocampal dysgenesis, with defects in the CA1-CA3 pyramidal cell layers and the dentate gyrus. TAp73 expression increases in parallel with neuronal differentiation and its ectopic expression induces neurite outgrowth and expression of neuronal markers in neuroblastoma cell lines and neural stem cells, suggesting that it has a pro-differentiation role. In contrast, ΔNp73 shows a survival function in mature cortical neurons as selective ΔNp73 null mice have reduced cortical thickness. Recent evidence has also suggested that p... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4567556 Mon, 07 Mar 2011 06:35:46 +0100 4567556 http://www.medworm.com/index.php?rid=4550593&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6579050133l06227%2F Abstract  Neuronal circuits with whisker-related patterns, such as those observed in the rodent somatosensory barrel cortex, have been widely used as a model system for investigating the anatomical organization, development and physiological roles of functional neuronal circuits. Whisker-related patterns exist not only in the barrel cortex but also in subcortical structures along the trigeminal neuraxis from the brainstem to the cortex. Here, we briefly summarize the organization, formation, and function of each neuronal circuit with whisker-related patterns, including the novel axonal trajectories that we recently found with the aid of in utero electroporation. We also discuss their biological implications as model systems for the studies of functional neuronal circuits. ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4550593 Wed, 02 Mar 2011 07:49:47 +0100 4550593 http://www.medworm.com/index.php?rid=4537420&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv6131128428714vv%2F Abstract  Numerous lines of evidence indicate that chronic inflammation plays a major role in the development of various neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, brain tumor, and meningitis. Why these diseases are more common among people from some countries than others is not fully understood, but lifestyle factors have been linked to the development of neurodegenerative diseases. For example, the incidence of certain neurodegenerative diseases among people living in the Asian subcontinent, where people regularly consume spices, is much lower than in countries of the western world. Extensive research over the last 10 years has indicated that nutraceuticals derived from such spices as turmeric, red pepper, ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4537420 Mon, 28 Feb 2011 06:39:54 +0100 4537420 http://www.medworm.com/index.php?rid=4523176&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe56162n3k4106262%2F Abstract  The songbird model is widely established in a number of laboratories for the investigation of the neurobiology and development of vocal learning. While vocal learning is rare in the animal kingdom, it is a trait that songbirds share with humans. The neuroanatomical and physiological organization of the brain circuitry that controls learned vocalizations has been extensively characterized, particularly in zebra finches (Taeniopygia guttata). Recently, several powerful molecular and genomic tools have become available in this organism, making it an attractive choice for neurobiologists interested in the neural and genetic basis of a complex learned behavior. Here, we briefly review some of the main features of vocal learning and associated brain structures in zebra f... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4523176 Tue, 22 Feb 2011 07:00:31 +0100 4523176 http://www.medworm.com/index.php?rid=4430234&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fgk473346812j7342%2F Abstract  Several sources of information suggest that human beings evolved on a diet that had a ratio of omega-6 to omega-3 fatty acids (FA) of about 1/1; whereas today, Western diets have a ratio of 10/1 to 20–25/1, indicating that Western diets are deficient in omega-3 FA compared with the diet on which humans evolved and their genetic patterns were established. Omega-6 and omega-3 FA are not interconvertible in the human body and are important components of practically all cell membranes. Studies with nonhuman primates and human newborns indicate that docosahexaenoic acid (DHA) is essential for the normal functional development of the brain and retina, particularly in premature infants. DHA accounts for 40% of the membrane phospholipid FA in the brain. Both eicosapenta... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4430234 Fri, 28 Jan 2011 20:43:53 +0100 4430234 http://www.medworm.com/index.php?rid=4416015&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl32u81587278q64t%2F Abstract  Collapsin response mediator protein-2 (DPYSL2 or CRMP2) is a multifunctional adaptor protein within the central nervous system. In the developing brain or cell cultures, CRMP2 performs structural and regulatory functions related to cytoskeletal dynamics, vesicle trafficking and synaptic physiology whereas CRMP2 functions in adult brain are still being elucidated. CRMP2 has been associated with several neuropathologic or psychiatric conditions including Alzheimer’s disease (AD) and schizophrenia, either at the level of genetic polymorphisms; protein expression; post-translational modifications; or protein/protein interactions. In AD, CRMP2 is phosphorylated by glycogen synthase kinase-3β (GSK3β) and cyclin dependent protein kinase-5 (CDK5), the same kinases tha... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4416015 Thu, 27 Jan 2011 10:02:52 +0100 4416015 http://www.medworm.com/index.php?rid=4416016&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc170015q364147g8%2F Abstract  The vascular network is closely linked to the neural system, and an interdependence is displayed in healthy and in pathophysiological responses. How has close apposition of two such functionally different systems occurred? Here, we present a hypothesis for the evolution of the vascular network from an ancestral neural guidance system. Biological cornerstones of this hypothesis are the vascular endothelial growth factor (VEGF) protein family and cognate receptors. The primary sequences of such proteins are conserved from invertebrates, such as worms and flies that lack discernible vascular systems compared to mammals, but all these systems have sophisticated neuronal wiring involving such molecules. Ancestral VEGFs and receptors (VEGFRs) could have been used to dev... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4416016 Thu, 27 Jan 2011 10:02:51 +0100 4416016 http://www.medworm.com/index.php?rid=4412746&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7w8573320n132xw2%2F Abstract  The consequences of fetal exposure to alcohol are very diverse and the likely molecular mechanisms involved must be able to explain how so many developmental processes could go awry. If pregnant rat dams are fed alcohol, their pups develop abnormalities characteristic of fetal alcohol spectrum disorders (FASD), but if these rat dams were also treated with choline, the effects from ethanol were attenuated in their pups. Choline is an essential nutrient in humans, and is an important methyl group donor. Alcohol exposure disturbs the metabolism of choline and other methyl donors. Availability of choline during gestation directly influences epigenetic marks on DNA and histones, and alters gene expression needed for normal neural and endothelial progenitor cell prolife... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4412746 Mon, 24 Jan 2011 06:38:38 +0100 4412746 http://www.medworm.com/index.php?rid=4364497&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl6nxnp5705264836%2F Abstract  Reactive astrocytes are associated with a vast array of central nervous system (CNS) pathologies. The activation of astrocytes is characterized by changes in their molecular and morphological features, and depending on the type of damage can also be accompanied by inflammatory responses, neuronal damage, and in severe cases, scar formation. Although reactive astrogliosis is the normal physiological response essential for containing damage, it can also have detrimental effects on neuronal survival and axon regeneration, particularly in neurodegenerative diseases. It is believed that progressive changes in astrocytes as they become reactive are finely regulated by complex intercellular and intracellular signaling mechanisms. However, these have yet to be sorted out.... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4364497 Sat, 15 Jan 2011 00:57:04 +0100 4364497 http://www.medworm.com/index.php?rid=4364498&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F458w880054826143%2F Abstract  Cognitive decline associated with ageing and age-related disorders emerges as one of the greatest health challenges in the next decades. To date, the molecular mechanisms underlying the onset of neuronal physiological changes in the central nervous system remain unclear. Functional MRI and PET studies have indicated the decline in working memory performance in older adults. Similarly, age-related disorders, such as Alzheimer’s disease, are associated with changes in the prefontral cortex and related neural circuitry, which underlines the decline of integrative function between different brain regions. This is mainly attributed to the loss of synaptic connectivity, which is a feature commonly observed in neurodegenerative disorders. In humans, the morphological a... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4364498 Sat, 15 Jan 2011 00:57:03 +0100 4364498 http://www.medworm.com/index.php?rid=4301258&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc641855767727568%2F Abstract  Synapse elimination is the main factor responsible for the cognitive decline accompanying many of the neuropathological conditions affecting humans. Synaptic stripping of motoneurons is also a common hallmark of several motor pathologies. Therefore, knowledge of the molecular basis underlying this plastic process is of central interest for the development of new therapeutic tools. Recent advances from our group highlight the role of nitric oxide (NO) as a key molecule triggering synapse loss in two models of motor pathologies. De novo expression of the neuronal isoform of NO synthase (nNOS) in motoneurons commonly occurs in response to the physical injury of a motor nerve and in the course of amyotrophic lateral sclerosis. In both conditions, this event precedes s... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4301258 Tue, 28 Dec 2010 20:46:02 +0100 4301258 http://www.medworm.com/index.php?rid=4282909&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb03m8650k2j1j243%2F Abstract  The cerebellum sits at the rostral end of the vertebrate hindbrain and is responsible for sensory and motor integration. Owing to its relatively simple architecture, it is one of the most powerful model systems for studying brain evolution and development. Over the last decade, the combination of molecular fate mapping techniques in the mouse and experimental studies, both in vitro and in vivo, in mouse and chick have significantly advanced our understanding of cerebellar neurogenesis in space and time. In amniotes, the most numerous cell type in the cerebellum, and indeed the brain, is the cerebellar granule neurons, and these are born from a transient secondary proliferative zone, the external granule layer (EGL), where proliferation is driven by sonic hedgehog ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4282909 Tue, 21 Dec 2010 07:21:33 +0100 4282909 http://www.medworm.com/index.php?rid=4268782&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fmr645l10628q8464%2F Abstract  Delayed vasospasm that develops 3–7 days after aneurysmal subarachnoid hemorrhage (SAH) has traditionally been considered the most important determinant of delayed ischemic injury and poor outcome. Consequently, most therapies against delayed ischemic injury are directed towards reducing the incidence of vasospasm. The clinical trials based on this strategy, however, have so far claimed limited success; the incidence of vasospasm is reduced without reduction in delayed ischemic injury or improvement in the long-term outcome. This fact has shifted research interest to the early brain injury (first 72 h) evoked by SAH. In recent years, several pathological mechanisms that activate within minutes after the initial bleed and lead to early brain injury are ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4268782 Wed, 15 Dec 2010 16:05:23 +0100 4268782 http://www.medworm.com/index.php?rid=4268785&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl28mv72075083223%2F Abstract  The promyeloctic leukemia protein PML is a tumor suppressor that was originally identified due to its involvement in the (15;17) translocation of acute promyelocytic leukemia. While the majority of early research has focused upon the role of PML in the pathogenesis of leukemia, more recent evidence has identified important roles for PML in tissues outside the hemopoietic system, including the central nervous system (CNS). Here, we review recent literature on the role of PML in the CNS, with particular focus on the processes of neurodevelopment and neurodegeneration, and propose new lines of investigation. Content Type Journal ArticleDOI 10.1007/s12035-010-8156-yAuthors Paolo Salomoni, Samantha Dickson Brain Cancer Unit, UCL Cancer Institute, Paul O’Gorman B... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4268785 Wed, 15 Dec 2010 16:05:22 +0100 4268785 http://www.medworm.com/index.php?rid=4268784&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv3x1x2u470r2w2x4%2F Abstract  Neuroglia is critically important for controlling the brain homeostasis and for mounting the brain defence against pathological insults. Here, we overview recent data about the role of neuroglia in various types of neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, fronto-temporal dementia, Wernicke encephalopathy, amyotrophic lateral sclerosis and immunodeficiency virus-1-associated dementia). In all these forms of neurodegeneration, astroglia undergoes complex morphological and functional changes. The early and mid-term stages of neurodegenerative processes, and specifically of Alzheimer’s disease, are associated with generalised atrophy of astroglia, whereas the later stages are characterised with an astrogliosis and microglial activatio... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4268784 Wed, 15 Dec 2010 16:05:22 +0100 4268784 http://www.medworm.com/index.php?rid=4268783&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd5k150737072n059%2F Abstract  Zinc is released from glutamatergic (zincergic) neuron terminals in the brain, followed by the increase in Zn2+ concentration in the intracellular (cytosol) compartment as well as that in the extracellular compartment. Intracellular Zn2+ concentration mainly increases through calcium-permeable channels and serves as Zn2+ signal as well as extracellular Zn2+ concentration. Hippocampal Zn2+ signaling may participate in synaptic plasticity such as long-term potentiation and cognitive function. On the other hand, subclinical zinc deficiency is common in the old who might be more susceptible to depression. Zinc deficiency causes abnormal glucocorticoid secretion and increases depression-like behavior in animals. Neuropsychological symptoms are observed prior to the decre... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4268783 Wed, 15 Dec 2010 16:05:22 +0100 4268783 http://www.medworm.com/index.php?rid=4250257&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F450072j3k243qg06%2F Abstract  Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder characterized by involuntary body movement, cognitive impairment and psychiatric disturbance. A polyglutamine expansion in the amino-terminal region of the huntingtin (htt) protein is the genetic cause of HD. Htt protein interacts with a wide variety of proteins, and htt mutation causes cell signaling alterations in various neurotransmitter systems, including dopaminergic, glutamatergic, and cannabinoid systems, as well as trophic factor systems. This review will overview recent findings concerning htt-promoted alterations in cell signaling that involve different neurotransmitters and trophic factor systems, especially involving mGluR1/5, as glutamate plays a crucial role in neuronal c... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4250257 Wed, 08 Dec 2010 17:43:29 +0100 4250257 http://www.medworm.com/index.php?rid=4227121&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb2k34384g55t066n%2F Abstract  Recent findings from genetic studies suggest that defective mitochondrial quality control may play an important role in the development of Parkinson's disease (PD). Such defects may result in the impairment of neuronal mitochondria, which leads to both synaptic dysfunction and cell death and results in neurodegeneration. Here, we review state-of-the-art knowledge of how pathways affecting mitochondrial quality control might contribute to PD, with a particular emphasis on the molecular mechanisms employed by PTEN-induced putative kinase 1 (PINK1), HtrA2 and Parkin to regulate mitochondrial quality control. Content Type Journal ArticleDOI 10.1007/s12035-010-8150-4Authors Inês Pimenta de Castro, Cell Death Regulation Laboratory, MRC Toxicology Unit, Hodgkin Bui... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4227121 Tue, 30 Nov 2010 17:55:14 +0100 4227121 http://www.medworm.com/index.php?rid=4209798&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fvu9668541w578547%2F Abstract  Meckel–Gruber syndrome (MKS) is a severe autosomal recessively inherited disorder characterized by developmental defects of the central nervous system that comprise neural tube defects that most commonly present as occipital encephalocele. MKS is considered to be the most common syndromic form of neural tube defect. MKS is genetically heterogeneous with six known disease genes: MKS1, MKS2/TMEM216, MKS3/TMEM67, RPGRIP1L, CEP290, and CC2D2A with the encoded proteins all implicated in the correct function of primary cilia. Primary cilia are microtubule-based organelles that project from the apical surface of most epithelial cell types. Recent progress has implicated the involvement of cilia in the Wnt and Shh signaling pathways and has led to an understanding of the... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4209798 Fri, 26 Nov 2010 07:07:40 +0100 4209798 http://www.medworm.com/index.php?rid=4193293&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F15g28v2381357h84%2F Abstract  Stimulating neuronal regeneration is a potential strategy to treat sight-threatening diseases of the retina. In some classes of vertebrates, retinal regeneration occurs spontaneously to effectively replace neurons lost to acute damage in order to restore visual function. There are different mechanisms and cellular sources of retinal regeneration in different species, include the retinal pigmented epithelium, progenitors seeded across the retina, and the Müller glia. This review briefly summarizes the different mechanisms of retinal regeneration in frogs, fish, chicks, and rodents. The bulk of this review summarizes and discusses recent findings regarding regeneration from Müller glia-derived progenitors, with emphasis on findings in the chick retina. The Müller... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4193293 Fri, 19 Nov 2010 07:38:30 +0100 4193293 http://www.medworm.com/index.php?rid=4193294&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq72050631960086g%2F Abstract  L-type Ca2+ channels (LTCCs, Cav1) open readily during membrane depolarization and allow Ca2+ to enter the cell. In this way, LTCCs regulate cell excitability and trigger a variety of Ca2+-dependent physiological processes such as: excitation–contraction coupling in muscle cells, gene expression, synaptic plasticity, neuronal differentiation, hormone secretion, and pacemaker activity in heart, neurons, and endocrine cells. Among the two major isoforms of LTCCs expressed in excitable tissues (Cav1.2 and Cav1.3), Cav1.3 appears suitable for supporting a pacemaker current in spontaneously firing cells. It has steep voltage dependence and low threshold of activation and inactivates slowly. Using Cav1.3−/− KO mice and membrane current recording techniques such as th... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4193294 Fri, 19 Nov 2010 07:38:29 +0100 4193294 http://www.medworm.com/index.php?rid=4187643&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk053h28467258348%2F Abstract  Mesencephalic and diencephalic dopaminergic (mdDA) progenitors generate two major groups of neurons corresponding to the A9 neurons of the substantia nigra pars compacta (SNpc) and the A10 neurons of the ventral tegmental area (VTA). MdDA neurons control motor, sensorimotor and motivated behaviour and their degeneration or abnormal functioning is associated to Parkinson’s disease and psychiatric disorders. Although relevant advances have been made, the molecular basis controlling identity, survival and vulnerability to neurodegeneration of SNpc and VTA neurons remains poorly understood. Here, we will review recent findings on the role exerted by the transcription factor Otx2 in adult mdDA neurons. Otx2 expression is restricted to a relevant fraction of VTA neuro... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4187643 Wed, 17 Nov 2010 20:58:18 +0100 4187643 http://www.medworm.com/index.php?rid=4176782&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr937505114225400%2F Abstract  The AMPA-type ionotropic glutamate receptors (AMPA-Rs) are tetrameric ligand-gated ion channels that play crucial roles in synaptic transmission and plasticity. Our knowledge about the ultrastructure and subunit assembly mechanisms of intact AMPA-Rs was very limited. However, the new studies using single particle EM and X-ray crystallography are revealing important insights. For example, the tetrameric crystal structure of the GluA2cryst construct provided the atomic view of the intact receptor. In addition, the single particle EM structures of the subunit assembly intermediates revealed the conformational requirement for the dimer-to-tetramer transition during the maturation of AMPA-Rs. These new data in the field provide new models and interpretations. In the br... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4176782 Mon, 15 Nov 2010 18:07:29 +0100 4176782 http://www.medworm.com/index.php?rid=4136556&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl35811346505rk7k%2F Abstract  Early in postnatal life γ-aminobutyric acid (GABA), the primary inhibitory transmitter in adults, excites targeted neurons by an outwardly directed flux of chloride which results from the unbalance between the cation–chloride cotransporters NKCC1 and KCC2, involved in chloride uptake and extrusion, respectively. This effect contributes to generate synchronized network activity or giant depolarizing potentials (GDPs) in the developing hippocampus. Here, we review some recent data concerning the mechanisms by which GDPs are generated and their functional role in enhancing synaptic efficacy at poorly developed GABAergic and glutamatergic synapses. In adulthood, reshaping neuronal circuits due to changes in chloride homeostasis and to the shift of GABA from hyperpo... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4136556 Tue, 02 Nov 2010 15:21:51 +0100 4136556 http://www.medworm.com/index.php?rid=4136557&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F266390321h4p3473%2F Abstract  Lead (Pb2+) is a ubiquitous environmental neurotoxicant that continues to threaten public health on a global scale. Epidemiological studies have demonstrated detrimental effects of Pb2+ on childhood IQ at very low levels of exposure. Recently, a mechanistic understanding of how Pb2+ affects brain development has begun to emerge. The cognitive effects of Pb2+ exposure are believed to be mediated through its selective inhibition of the N-methyl-d -aspartate receptor (NMDAR). Studies in animal models of developmental Pb2+ exposure exhibit altered NMDAR subunit ontogeny and disruption of NMDAR-dependent intracellular signaling. Additional studies have reported that Pb2+ exposure inhibits presynaptic calcium (Ca2+) channels and affects presynaptic neurotransmission, but a... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4136557 Mon, 01 Nov 2010 17:59:31 +0100 4136557 http://www.medworm.com/index.php?rid=4042452&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5333291911211567%2F Abstract  The family of calcium-dependent neutral proteases, calpains, was discovered more than 30 years ago, but their functional roles in the nervous system under physiological or pathological conditions still remain unclear. Although calpain was proposed to participate in synaptic plasticity and in learning and memory in the early 1980s, the precise mechanism regarding its activation, its target(s) and the functional consequences of its activation have remained controversial. A major issue has been the identification of roles of the two major calpain isoforms present in the brain, calpain-1 and calpain-2, and the calcium requirement for their activation, which exceeds levels that could be reached intracellularly under conditions leading to changes in synaptic effica... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4042452 Tue, 05 Oct 2010 18:09:27 +0100 4042452 http://www.medworm.com/index.php?rid=4006803&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl174q25j281j8664%2F Abstract  Many lines of evidence indicate the importance of the Rho family guanine nucleotide triphosphatases (GTPases) in directing axon extension and guidance. The signaling networks that involve these proteins regulate actin cytoskeletal dynamics in navigating neuronal growth cones. However, the intricate patterns that regulate Rho GTPase activation and signaling are not yet fully defined. Activity and subcellular localization of the Rho GTPases are regulated by post-translational modification. The addition of a geranylgeranyl group to the carboxy (C-) terminus targets Rho GTPases to the plasma membrane and promotes their activation by facilitating interaction with guanine nucleotide exchange factors and allowing sequestering by association with guanine dissociation inhi... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=4006803 Mon, 27 Sep 2010 16:52:35 +0100 4006803 http://www.medworm.com/index.php?rid=3668816&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq5238k8w55522431%2F Abstract  Apoptosis was a term introduced in 1972 to distinguish a mode of cell death with characteristic morphology and apparently regulated, endogenously driven mechanisms. The effector processes responsible for apoptosis are now mostly well known, involving activation of caspases and Bcl2 family members in response to a wide variety of physiological and injury-induced signals. The factors that lead of the decision to activate apoptosis as opposed to adaptive responses to such signals (e.g. autophagy, cycle arrest, protein synthesis shutoff) are less well understood, but the intranuclear Promyelocytic Leukaemia Body (PML body) may create a local microenvironment in which the audit of DNA damage may occur, informed by the extent of the damage, the adequacy of its repair an... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3668816 Wed, 16 Jun 2010 07:18:33 +0100 3668816 http://www.medworm.com/index.php?rid=3627574&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc63671206250v274%2F Abstract  Heat shock proteins (Hsps) are highly conserved proteins that are induced in response to various physiological and environmental stressors. HspB1 (Hsp27) is a prominent member of the small Hsps family and is strongly induced during the stress response. Notably, HspB1 has powerful neuroprotective effects, increasing the survival of cells subjected to cytotoxic stimuli. This is especially relevant to the study of the retina, where cells are subject to death due to retinal disease and injury. While HspB1 shows constitutive expression in some areas of the mammalian retina, of particular interest is the upregulation of the protein in response to ischemia and oxidative stress, traumatic nerve injury, and elevated intraocular pressure and glaucoma. Several mechanisms hav... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3627574 Tue, 01 Jun 2010 11:04:03 +0100 3627574 http://www.medworm.com/index.php?rid=3579375&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd82x7044k0862m83%2F Content Type Journal ArticleDOI 10.1007/s12035-010-8140-6Authors H. Anne Leaver, University of Edinburgh Department of Clinical Neurosciences Edinburgh UKGiles Hardingham, University of Edinburgh Centre for Neuroscience Research Edinburgh UK Journal Molecular NeurobiologyOnline ISSN 1559-1182Print ISSN 0893-7648 (Source: Molecular Neurobiology) Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3579375 Tue, 18 May 2010 08:17:28 +0100 3579375 http://www.medworm.com/index.php?rid=3579376&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv360181412849421%2F Abstract  Although neuronal cell death through apoptotic pathways represents a common feature of dysferopathies, the canonical apoptotic changes familiar from nonneuronal cells are late events. Loss of neuronal function occurs at a much early time, when synaptic-based neuronal connectivity fails. In this context, apoptotic pathways may normally serve a cleanup role, rather than a pathogenic one. Reframing the consideration of cell death in the nervous system to include the early stages of axonal degeneration provides a better understanding of the roles played by various apoptotic signaling pathways in neurodegenerative diseases. Focusing on disease-specific mechanisms that initiate the sequence that eventually leads to neuronal loss should facilitate development of therapie... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3579376 Tue, 18 May 2010 08:17:27 +0100 3579376 http://www.medworm.com/index.php?rid=3567562&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa122418603571570%2F Abstract  A number of intrinsic factors are present intracellularly and could be turned on to protect cells from stress and injury, including cerebral ischemia. The degree of protection of these factors is dependent on the time of induction, their concentration, as well as the duration and extent of injury. This review summarizes recent studies on some of the protective factors with specific emphasis on two recently discovered intrinsic protective proteins: 14-3-3γ protein and neuroglobin. Both of them were originally discovered in neurons, later identified in astrocytes under ischemic conditions, and demonstrated to have protective effect on nerve cells from apoptosis. Understanding the mode of induction and role of protection of these intrinsic protective proteins would ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3567562 Fri, 14 May 2010 09:36:26 +0100 3567562 http://www.medworm.com/index.php?rid=3567561&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj247865q32183660%2F Abstract  The significance of the selective enrichment in omega-3 essential fatty acids in photoreceptors and synaptic membranes of the nervous system has remained, until recently, incompletely understood. While studying mechanisms of cell survival in neural degeneration, we discovered a docosanoid synthesized from unesterified docosahexaenoic acid (DHA) by a 15-lipoxygenase (15-LOX), which we called neuroprotectin D1 (NPD1; 10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15E,19Z hexaenoic acid). This lipid mediator is a docosanoid because it is derived from the 22 carbon (22C) precursor DHA, unlike eicosanoids, which are derived from the 20 carbon (20C) arachidonic acid (AA) family member of essential fatty acids. We discovered that NPD1 is promptly made in response to oxidative str... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3567561 Fri, 14 May 2010 09:36:26 +0100 3567561 http://www.medworm.com/index.php?rid=3562118&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F854811q43822tun7%2F Abstract  As a fully differentiated organ, our brain is very sensitive to cumulative oxidative damage of proteins, lipids, and DNA occurring during normal aging because of its high energy metabolism and the relative low activity of antioxidative defense mechanisms. As a major consequence, perturbations of energy metabolism including mitochondrial dysfunction, alterations of signaling mechanisms and of gene expression culminate in functional deficits. With the increasing average life span of humans, age-related cognitive disorders such as Alzheimer’s disease (AD) are a major health concern in our society. Age-related mitochondrial dysfunction underlies most neurodegenerative diseases, where it is potentiated by disease-specific factors. AD is characterized by two major his... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3562118 Wed, 12 May 2010 07:04:09 +0100 3562118 http://www.medworm.com/index.php?rid=3540430&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl71v7706n5r89205%2F Abstract  The prognosis for patients with malignant gliomas is poor, but improvements may emerge from a better understanding of the pathophysiology of glioma signalling. Recent therapeutic developments have implicated lipid signalling in glioma cell death. Stress signalling in glioma cell death involves mitochondria and endoplasmic reticulum. Lipid mediators also signal via extrinsic pathways in glioma cell proliferation, migration and interaction with endothelial and microglial cells. Glioma cell death and tumour regression have been reported using polyunsaturated fatty acids in animal models, human ex vivo explants, glioma cell preparations and in clinical case reports involving intratumoral infusion. Cell death signalling was associated with generation of reactive oxygen... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3540430 Wed, 05 May 2010 07:57:12 +0100 3540430 http://www.medworm.com/index.php?rid=3532111&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5n725vht35510j70%2F Abstract  Alzheimer's disease is a chronic neurodegenerative disorder characterized by neuronal loss, cerebrovascular inflammation, and accumulation of senile plaques in the brain parenchyma and cerebral blood vessels. Amyloid-β peptide (Aβ), a major component of senile plaques, has been shown to exert multiple toxic effects to neurons, astrocytes, glial cells, and brain endothelium. Oligomeric Aβ can disturb the structure and function of cell membranes and alter membrane mechanical properties, such as membrane fluidity and molecular order. Much of these effects are attributed to their capability to trigger oxidative stress and inflammation. In this review, we discuss the effects of Aβ on neuronal cells, astrocytes, and cerebral endothelial cells with special emphasis o... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3532111 Sat, 01 May 2010 07:13:45 +0100 3532111 http://www.medworm.com/index.php?rid=3532112&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fcw46185086x91258%2F Abstract  Alzheimer's disease (AD) involves a complex pathological cascade thought to be initially triggered by the accumulation of β-amyloid (Aβ) peptide aggregates or aberrant amyloid precursor protein (APP) processing. Much is known of the factors initiating the disease process decades prior to the onset of cognitive deficits, but an unclear understanding of events immediately preceding and precipitating cognitive decline is a major factor limiting the rapid development of adequate prevention and treatment strategies. Multiple pathways are known to contribute to cognitive deficits by disruption of neuronal signal transduction pathways involved in memory. These pathways are altered by aberrant signaling, inflammation, oxidative damage, tau pathology, neuron loss, and sy... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3532112 Sat, 01 May 2010 07:13:44 +0100 3532112 http://www.medworm.com/index.php?rid=3523622&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ftv08152717725n14%2F Abstract  The capacity to generate myriad differentiated cell types, including neurons, from human embryonic stem (hES) cell lines offers great potential for developing cell-based therapies and also for increasing our understanding of human developmental mechanisms. In addition, the emerging development of this technology as an experimental tool represents a potential opportunity for neuroscientists interested in mechanisms of neuroprotection and neurodegeneration. Potentially unlimited generation of well-defined functional neurons from hES and patient-specific induced pluripotent cells offers new systems to study disease mechanisms, signalling pathways and receptor pharmacology within a human cellular environment. Such systems may help in overcoming interspecies differences... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3523622 Thu, 29 Apr 2010 21:16:03 +0100 3523622 http://www.medworm.com/index.php?rid=3523623&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj541198k75002364%2F Abstract  Polyunsaturated fatty acids (PUFAs) are known to inhibit cell proliferation of many tumour types both in vitro and in vivo. Their capacity to interfere with cell proliferation has been linked to their induction of reactive oxygen species (ROS) production in tumour tissues leading to cell death through apoptosis. However, the exact mechanisms of action of PUFAs are far from clear, particularly in brain tumours. The loss of bound hexokinase from the mitochondrial voltage-dependent anion channel has been directly related to loss of protection from apoptosis, and PUFAs can induce this loss of bound hexokinase in tumour cells. Tumour cells overexpressing Akt activity, including gliomas, are sensitised to ROS damage by the Akt protein and may be good targets for chemoth... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3523623 Thu, 29 Apr 2010 21:16:01 +0100 3523623 http://www.medworm.com/index.php?rid=3523624&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F27517563227731t2%2F Abstract  Platelet-activating factor (PAF) is a potent bioactive lipid generated in the cornea after injury whose actions are mediated through specific receptors. Studies from our laboratory have shown that PAF interactions with its receptors activate several transmembrane signals involved in apoptosis. Continuous exposure to PAF during prolonged inflammation increases keratocyte apoptosis and inhibition of epithelial adhesion to the basement membrane. As a consequence, there is a marked delay in wound healing, which is not countered by the action of growth factors. While apoptosis of stroma cells is rapid and potent, epithelial cells as well as myofibroblasts, which appear in the stroma during the repair phase, are resistant to apoptosis. However, PAF accelerates apoptosis... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3523624 Thu, 29 Apr 2010 21:15:59 +0100 3523624 http://www.medworm.com/index.php?rid=3517191&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb277836q22rr1847%2F Abstract  The benefits of programmed cell death by apoptosis are the safe and efficient clearance of damaged, infected, or surplus cells, primarily mediated by tissue-resident macrophages or tissue-infiltrating blood monocytes that differentiate into macrophages. Microglial cells are macrophages of the brain parenchyma, important immune surveillance cells that respond to various injuries and diseases of the brain. It is often stated that how a macrophage interacts with an apoptotic cell defines subsequent inflammatory responses, i.e., will engulfment be beneficial or detrimental for tissue repair, regeneration, and immunity. Our focus has been to better understand how macrophages discriminate between living and dying cells. Following our initial findings with platelet endot... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3517191 Wed, 28 Apr 2010 08:31:02 +0100 3517191 http://www.medworm.com/index.php?rid=3513346&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8u13416177t51w75%2F Abstract  Docosahexaenoic acid (DHA), the end-product of the metabolism of omega-3 family fatty acids, is the main polyunsaturated fatty acid of the brain, but its accumulation is incompletely understood. This paper reviews how it could accumulate through specific uptake of DHA-containing lysophosphatidylcholine (LysoPC-DHA). DHA migrates very easily from the sn-2 position of LysoPC, which could be considered as the physiological form of polyunsaturated LysoPC, to the sn-1 position, which is much more stable. An approach preventing migration by acetylating the sn-1 position, while retaining the main physico-chemical properties of the carrier, is described. Also, the double lipoxygenation and bond-isomerization of DHA into 10(S),17(S)-docosahexa-4Z,7Z,11E,13Z,15E,19Z-enoic acid... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3513346 Tue, 27 Apr 2010 07:04:23 +0100 3513346 http://www.medworm.com/index.php?rid=3513347&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff21t61863tq38p43%2F Abstract  There is no question that chronic alcohol (ethanol) abuse, a leading worldwide problem, causes neuronal dysfunction and brain damage. However, various epidemiologic studies in recent years have indicated that in comparisons with abstainers or never-drinkers, light/moderate alcohol consumers have lower risks of age-dependent cognitive decline and/or dementia, including Alzheimer’s disease (AD). Such reduced risks have been variously attributed to favorable circulatory and/or cerebrovascular effects of moderate ethanol intake, but they could also involve ethanol “preconditioning” phenomena in brain glia and neurons. Here we summarize our experimental studies showing that moderate ethanol preconditioning (MEP; 20–30 mM ethanol) of rat brain cultures prev... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3513347 Tue, 27 Apr 2010 07:04:22 +0100 3513347 http://www.medworm.com/index.php?rid=3502293&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu71846x412rlx751%2F Abstract  It has long been recognised that malignant tumours favour aerobic glycolysis to generate ATP and contain abnormalities of the intrinsic, mitochondria-dependent, apoptotic pathway, suggesting the involvement of dysfunctional mitochondria in tumour pathophysiology. However, the mechanisms underlying such processes in gliomas are poorly understood. Few recent studies have evaluated mitochondrial ultrastructure and proteomics in the pathophysiology of malignant gliomas. However, aberrant energy metabolism has been reported in gliomas and mitochondrial dysfunction links to glioma apoptotic signalling have been observed. Mitochondrial structural abnormalities and dysfunction in malignant gliomas is a neglected area of research. Definition of abnormalities in mitochondri... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3502293 Fri, 23 Apr 2010 08:32:30 +0100 3502293 http://www.medworm.com/index.php?rid=3502294&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fkt3025g4k736035n%2F Abstract  Aging is associated with an enhanced susceptibility to brain dysfunction, loss of memory, and cognitive decline and significantly influences the quality of life for the affected individual. Recent molecular–genetic approaches have provided powerful insights into common age-related diseases that are both progressive and multifactorial, such as Alzheimer’s disease (AD), and in vitro in AD models. These investigations have uncovered consistent deficits in brain gene signaling mechanisms and neurotrophic substances known to contribute to normal brain function. Inflammatory signaling pathways involving up-regulation of cytosolic phospholipase A2 and the arachidonic acid cycle, the depletion of the brain-essential fatty acid docosahexaenoic acid (DHA) and DHA-derived... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3502294 Fri, 23 Apr 2010 08:32:27 +0100 3502294 http://www.medworm.com/index.php?rid=3502295&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3m6777k36471q676%2F Abstract  The biological roles of poly(ADP-ribose) polymers (PAR) and poly(ADP-ribosyl)ation of proteins in the central nervous system are diverse. The homeostasis of PAR orchestrated by poly(ADP-ribose) polymerase-1 (PARP-1) and poly(ADP-ribose) glycohydrolase (PARG) is crucial for cell physiology and pathology. Both enzymes are ubiquitously distributed in neurons and glia; however, they are segregated at the subcellular level. PARP-1 serves as a “nick sensor” for single- or double-stranded breaks in DNA and is involved in long and short patch base-excision repair, while PARG breaks down PAR. The stimulation of PARP-1 and PAR formation can activate proinflammatory transcription factors, including nuclear factor kappa B. However, hyperactivation of PARP-1 can result in ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3502295 Thu, 22 Apr 2010 09:28:40 +0100 3502295 http://www.medworm.com/index.php?rid=3502296&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj2655351523uhxu4%2F Abstract  Myoclonic epilepsy and ragged-red fibers (MERRF) syndrome is a rare disorder characterized by myoclonus, muscle weakness, cerebellar ataxia, heart conduction block, and dementia. It has been documented that 80–90% of the patients with MERRF syndrome are caused by the A8344G mutation in the tRNALys gene of mitochondrial DNA (mtDNA). We and other investigators have reported that the mtDNA mutation results in not only inefficient generation of adenosine triphosphate but also increased production of reactive oxygen species (ROS) in cultured cells harboring A8344G mutation of mtDNA. In addition, we found an imbalance in the gene expression of antioxidant enzymes in the skin fibroblasts of MERRF patients. The mRNA, protein, and enzyme activity levels of manganese-super... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3502296 Thu, 22 Apr 2010 09:28:39 +0100 3502296 http://www.medworm.com/index.php?rid=3496071&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fkn27742183136x52%2F Abstract  Emerging evidence indicates that brain microvascular endothelial cells play a critical role in brain development, maturation, and homeostasis. Acute or chronic insults, including oxidative stress, oxygen–glucose deprivation, trauma, infections, inflammatory cytokines, DNA damaging agents, β-amyloid deposition, and endoplasmic reticulum stress induce brain endothelial cell dysfunction and damage, which can result in cell death. The homeostatic balance between endothelial cell survival and endothelial cell death is critical for brain development, remodeling, and repair. On the other hand, dysregulation of brain endothelial cell death exacerbates, or even initiates, several inflammatory, ischemic, and degenerative disorders of the central nervous system. In here, ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3496071 Wed, 21 Apr 2010 09:24:41 +0100 3496071 http://www.medworm.com/index.php?rid=3496070&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu23454852h288287%2F This article describes recent studies that link the photoactivation of rhodopsin to tyrosine phosphorylation of the IR and subsequent activation of phosphoinositide 3-kinase, a neuron survival factor. Our studies suggest that the physiological role of this process is to provide neuroprotection of the retina against light damage by activating proteins that protect against stress-induced apoptosis. We focus mainly on our recently identified regulation of the IR pathway through the G-protein-coupled receptor rhodopsin. Various mutant and knockout proteins of phototransduction cascade have been used to study the light-induced activation of the retinal IR. Our studies suggest that rhodopsin may have additional previously uncharacterized signaling functions in photoreceptors. Content ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3496070 Wed, 21 Apr 2010 09:24:41 +0100 3496070 http://www.medworm.com/index.php?rid=3492278&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv7656002nu175578%2F Abstract  The neuroprotective effects of granulocyte colony-stimulating factor (G-CSF) were reported in several neurological disease models, including Parkinson’s disease (PD). In the present study, we investigated the therapeutic effect of G-CSF after the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD was established. G-CSF was subcutaneously administered into C57BL/6 mice that had undergone systemic MPTP injections. We found that G-CSF treatment markedly increased the number of dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the G-CSF-treated group. Consistent with this finding, we found a significant increase in dopamine release under high K+ stimulation in the striatum of the G-CSF-treated animals compared to the MPTP-exposed... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3492278 Tue, 20 Apr 2010 11:21:14 +0100 3492278 http://www.medworm.com/index.php?rid=3492277&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F575182n908323r11%2F Abstract  Recently, one of the P2 purinergic receptors, the P2X7 receptor, has been extensively studied in nervous system and important functions have been revealed in both astrocytes and microglia. Stimulation of the receptors induces a sustained and nondesensitized increase in intracellular Ca2+ concentration ([Ca2+]i). In astrocytes purinergic receptors primarily regulate neurotransmission by inducing gliotransmitters release whereas in microglia the receptors stimulate the processing and release of proinflammation cytokines such as interleukin-1 and are thereby involved in inflammation and neurodegeneration. Thus, P2X7 receptors are considered not only to exert physiological functions but also mediate cell death. P2X7 receptors have also been identified in various cancer c... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3492277 Tue, 20 Apr 2010 11:21:14 +0100 3492277 http://www.medworm.com/index.php?rid=3492276&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fdrt87607ph122643%2F Abstract  There is keen interest in the role of the isoprenoids farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP) in protein prenylation and cell function in Alzheimer’s disease (AD). We recently reported elevated FPP and GGPP brain levels and increased gene expression of FPP synthase (FPPS) and GGPP synthase (GGPPS) in the frontal cortex of AD patients. Cholesterol levels and gene expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase were similar in AD and control samples, suggesting that homeostasis of FPP and GGPP but not cholesterol is specifically targeted in brain tissue of AD patients (Neurobiol Dis 2009 35:251–257). In the present study, it was determined if cellular levels of FPP, GGPP, and cholesterol affect beta-amyloid (Aβ) abundanc... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3492276 Tue, 20 Apr 2010 11:21:14 +0100 3492276 http://www.medworm.com/index.php?rid=3469707&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2580225n13325841%2F Content Type Journal ArticleDOI 10.1007/s12035-010-8119-3Authors Grace Y. Sun, University of Missouri Biochemistry Department 117 Schweitzer Hall Columbia MO USAW. Gibson Wood, University of Minnesota Department of Pharmacology Minneapolis MN USA Journal Molecular NeurobiologyOnline ISSN 1559-1182Print ISSN 0893-7648 (Source: Molecular Neurobiology) Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3469707 Mon, 12 Apr 2010 17:59:05 +0100 3469707 http://www.medworm.com/index.php?rid=3469706&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa75296542232u05q%2F Abstract  Acute inflammation is important for tissue repair; however, chronic inflammation contributes to neurodegeneration in Alzheimer's disease (AD) and occurs when glial cells undergo prolonged activation. In the brain, stress or damage causes the release of nucleotides and activation of the Gq protein-coupled P2Y2 nucleotide receptor subtype (P2Y2R) leading to pro-inflammatory responses that can protect neurons from injury, including the stimulation and recruitment of glial cells. P2Y2R activation induces the phosphorylation of the epidermal growth factor receptor (EGFR), a response dependent upon the presence of a SH3 binding domain in the intracellular C terminus of the P2Y2R that promotes Src binding and transactivation of EGFR, a pathway that regulates the proliferat... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3469706 Mon, 12 Apr 2010 17:59:05 +0100 3469706 http://www.medworm.com/index.php?rid=3451514&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F507k1113vv101131%2F We report novel findings showing that up-regulation of Bcl-2 by simvastatin involves ET-1 and the transcription factor NFATc3. Discovering how statins can selectively alter a specific NFATc isoform that leads to an increase in an antiapoptotic protein will provide a new approach to understanding statin-induced neuroprotection and conditions outside the brain in which apoptosis contributes to pathophysiology. Content Type Journal ArticleDOI 10.1007/s12035-010-8122-8Authors Tammy A. Butterick, University of Minnesota Department of Pharmacology, Geriatric Research Education and Clinical Center, VA Medical Center Minneapolis MN USAUrule Igbavboa, University of Minnesota Department of Pharmacology, Geriatric Research Education and Clinical Center, VA Medical Center Minneapolis MN USAG... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3451514 Mon, 05 Apr 2010 21:36:26 +0100 3451514 http://www.medworm.com/index.php?rid=3431107&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn70548010775r170%2F Abstract  Heat shock protein 70 (Hsp70) plays important roles in neural protection from stress by assisting cellular protein folding. In this review we discuss the current understanding of inducible and constitutive Hsp70 in maintaining and protecting neuronal synaptic function under normal and stressed conditions. Content Type Journal ArticleDOI 10.1007/s12035-010-8116-6Authors Tom Z. Lu, University of Toronto Department of Physiology 3306 MSB, 1 King’s College Circle Toronto Ontario Canada M5S 1A8Yi Quan, University of Toronto Department of Physiology 3306 MSB, 1 King’s College Circle Toronto Ontario Canada M5S 1A8Zhong-Ping Feng, University of Toronto Department of Physiology 3306 MSB, 1 King’s College Circle Toronto Ontario Canada M5S 1A8 Journal Molecul... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3431107 Wed, 31 Mar 2010 05:56:29 +0100 3431107 http://www.medworm.com/index.php?rid=3406053&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fdr2841q74822lk72%2F Abstract  Overstimulation of N-methyl-d-aspartate (NMDA)-type glutamate receptors accounts, at least in part, for excitotoxic neuronal damage, potentially contributing to a wide range of acute and chronic neurologic diseases. Neurodegenerative disorders including Alzheimer’s disease (AD) and Parkinson’s disease (PD), manifest deposits of misfolded or aggregated proteins, and result from synaptic injury and neuronal death. Recent studies have suggested that nitrosative stress due to generation of excessive nitric oxide (NO) can mediate excitotoxicity in part by triggering protein misfolding and aggregation, and mitochondrial fragmentation in the absence of genetic predisposition. S-Nitrosylation, or covalent reaction of NO with specific protein thiol groups, represents a ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3406053 Wed, 24 Mar 2010 05:47:07 +0100 3406053 http://www.medworm.com/index.php?rid=3392564&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff7x3486223786685%2F Abstract  Excess production of reactive oxygen species in the brain has been implicated as a common underlying risk factor for the pathogenesis of a number of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In recent years, there is considerable interest concerning investigation of antioxidative and anti-inflammatory effects of phenolic compounds from different botanical sources. In this review, we first describe oxidative mechanisms associated with stroke, AD, and PD, and subsequently, we place emphasis on recent studies implicating neuroprotective effects of resveratrol, a polyphenolic compound derived from grapes and red wine. These studies show that the beneficial effects of resveratrol are not only limited to its a... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3392564 Sun, 21 Mar 2010 05:50:35 +0100 3392564 http://www.medworm.com/index.php?rid=3386451&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F783u685q8t4p4423%2F Abstract  Several “low molecular weight” or “secretory” phospholipases A2 isoforms may be expressed in mammalian neural cells. Indeed, mRNAs for GIB, GIIA, GIIE, GIII, GV, GX, and GXII were detected in brain tissues despite different levels. However, only the presence of GIB, GIIA, and GV proteins has been clearly demonstrated in neural cells or in the nervous tissue. Although the roles of GIB and GV in the nervous tissue are still elusive, there is evidence to support the involvement of GIIA in physiological and pathological events, including neurotransmission, long-term potentiation, and neuritogenesis. The neurotoxic effects of an increase in GIIA may be envisaged under pathological conditions associated with the activation of astrocytes during inflammation or thr... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3386451 Thu, 18 Mar 2010 15:40:05 +0100 3386451 http://www.medworm.com/index.php?rid=3376174&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc5p285t427g2v707%2F Abstract  Oxidative stress has been linked to various physiological and pathological processes such as aging and neurological disorders. Recent evidence has now implicated a role for oxidative stress in sleep and sleep loss. Studies suggest that wakefulness results in an oxidative burden and sleep provides a protective mechanism against these harmful effects. Prolonged wakefulness/sleep deprivation activates an adaptive stress pathway termed the unfolded protein response (UPR), which temporarily guards against the deleterious consequences of reactive oxygen species. The UPR affects the function of the endoplasmic reticulum, which is the site for integral and secretory membrane processing and folding. Several downstream effectors of the UPR operate in an antioxidant capacity... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3376174 Tue, 16 Mar 2010 14:52:51 +0100 3376174 http://www.medworm.com/index.php?rid=3361046&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff5n6258g6433741t%2F Abstract  The accumulation of arginine in the cerebrospinal fluid and brains of patients suffering from acute neurodegenerative diseases like Alzheimer’s disease, point to defects in the metabolic pathways involving this amino acids. The deposits of neurofibrillary tangles and senile plaques perhaps as a consequence of fibrillogenesis of β-amyloid peptides has also been shown to be a hallmark in the aetiology of certain neurodegenerative diseases. Peptidylarginine deiminase (PAD II) is an enzyme that uses arginine as a substrate and we now show that PAD II not only binds with the peptides Aβ1-40, Aβ22-35, Aβ17-28, Aβ25-35 and Aβ32-35 but assists in the proteolytic degradation of these peptides with the concomitant formation of insoluble fibrils. PAD was purified in 1... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3361046 Thu, 11 Mar 2010 18:26:46 +0100 3361046 http://www.medworm.com/index.php?rid=3361047&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2l7v6571737264nw%2F Abstract  The protein adduct carboxyethylpyrrole (CEP) is present in age-related macular degeneration (AMD) eye tissue and in the blood of AMD patients at higher levels than found in age-matched non-AMD tissues. Autoantibodies to CEP are also higher in AMD blood samples than in controls. To test the hypothesis that this hapten is causally involved in initiating an inflammatory response in AMD, we immunized C57BL/6J mice with mouse serum albumin (MSA) adducted with CEP. Immunized mice develop antibodies to CEP, fix complement component-3 in Bruch’s membrane, accumulate drusen below the retinal pigment epithelium during aging, show decreased a- and b-wave amplitudes in response to light, and develop lesions in the retinal pigment epithelium mimicking geographic atrophy, the... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3361047 Thu, 11 Mar 2010 06:49:59 +0100 3361047 http://www.medworm.com/index.php?rid=3356478&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4q715g5842528x57%2F Abstract  The histopathological characteristics of Alzheimer’s disease (AD) are amyloid-β (Aβ) containing plaques and neurofibrillary tangles (NFTs) as well as neuronal and synaptic loss. Until today, the underlying mechanisms of the interplay of plaques and tangles remained unresolved. There is increasing evidence that mitochondrial dysfunction might be a possible link, as revealed by studies in several APP and tau transgenic mouse models. Recently, we examined mitochondrial function in a novel triple transgenic mouse model (pR5/APP/PS2)—tripleAD mice—that combines both pathologic features of the disease in brain. Using comparative, quantitative proteomics (iTRAQ) and mass spectroscopy, we found a massive deregulation of 24 proteins, of which one third were mitochon... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3356478 Wed, 10 Mar 2010 15:33:10 +0100 3356478 http://www.medworm.com/index.php?rid=3356477&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc7j8465255330600%2F Abstract  Cyclic guanosine monophosphate (cGMP) is an important secondary messenger synthesized by the guanylyl cyclases which are found in the soluble (sGC) and particular isoforms. In the central nervous system, the nitric oxide (NO)-sensitive sGC isoform is the major enzyme responsible for cGMP synthesis. Phosphodiesterases (PDEs) are enzymes for hydrolysis of cGMP in the brain, and they are mainly isoforms 2, 5, and 9. The NO/cGMP signaling pathway has been shown to play an important role in the process underlying learning and memory. Aging is associated with an increase in PDE expression and activity and a decrease in cGMP concentration. In addition, aging is also associated with an enhancement of neuronal NO synthase, a lowering of endothelial, and no alteration in in... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3356477 Wed, 10 Mar 2010 15:33:10 +0100 3356477 http://www.medworm.com/index.php?rid=3329005&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu2744756m35k7827%2F Abstract  Alzheimer’s disease (AD) is marked by an increase in the production of extracellular beta amyloid plaques and intracellular neurofibrillary tangles associated with a decline in brain function. Increases in oxidative stress are regarded as an early sign of AD pathophysiology, although the source of reactive oxygen species (ROS) and the mechanism(s) whereby beta amyloid peptides (Aβ) impact oxidative stress have not been adequately investigated. Recent studies provide strong evidence for the involvement of NADPH oxidase and its downstream oxidative signaling pathways in the toxic effects elicited by Aβ. ROS produced by NADPH oxidase activate multiple signaling pathways leading to neuronal excitotoxicity and glial cell-mediated inflammation. This review describes... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3329005 Tue, 02 Mar 2010 10:07:43 +0100 3329005 http://www.medworm.com/index.php?rid=3329006&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb54l38q5g836g936%2F Abstract  Inflammatory neurodegeneration contributes to a wide variety of brain pathologies. A number of mechanisms by which inflammatory-activated microglia and astrocytes kill neurons have been identified in culture. These include: (1) acute activation of the phagocyte NADPH oxidase (PHOX) found in microglia, (2) expression of the inducible nitric oxide synthase (iNOS) in glia, and (3) microglial phagocytosis of neurons. Activation of PHOX (by cytokines, β-amyloid, prion protein, lipopolysaccharide, ATP, or arachidonate) causes microglial proliferation and inflammatory activation; thus, PHOX is a key regulator of inflammation. However, activation of PHOX alone causes little or no death, but when combined with iNOS expression results in apparent apoptosis via peroxynitrite... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3329006 Tue, 02 Mar 2010 10:07:41 +0100 3329006 http://www.medworm.com/index.php?rid=3329007&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa1v7p5w635m81380%2F Abstract  Inflammatory regulators, including endogenous anti-inflammatory systems, can down-regulate inflammation thus providing negative feedback. Chronic inflammation can result from imbalance between levels of inflammatory mediators and regulators during immune responses. As a consequence, there are heightened inflammatory responses and irreversible tissue damage associated with many age-related chronic diseases. Alzheimer’s disease (AD) brain is marked by prominent inflammatory features, in which microglial activation is the driving force for the elaboration of an inflammatory cascade. How the regulation of inflammation loses its effectiveness during AD pathogenesis remains largely unclear. In this article, we will first review current knowledge of microglial activati... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3329007 Tue, 02 Mar 2010 10:07:40 +0100 3329007 http://www.medworm.com/index.php?rid=3281522&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn12p947705803657%2F Abstract  Effective stroke therapies require recanalization of occluded cerebral blood vessels. However, reperfusion can cause neurovascular injury, leading to cerebral edema, brain hemorrhage, and neuronal death by apoptosis/necrosis. These complications, which result from excess production of reactive oxygen species in mitochondria, significantly limit the benefits of stroke therapies. We have developed a focal stroke model using mice deficient in mitochondrial manganese-superoxide dismutase (SOD2−/+) to investigate neurovascular endothelial damage that occurs during reperfusion. Following focal stroke and reperfusion, SOD2−/+ mice had delayed blood-brain barrier breakdown, associated with activation of matrix metalloproteinase and high brain hemorrhage rates, whereas... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3281522 Tue, 16 Feb 2010 06:45:00 +0100 3281522 http://www.medworm.com/index.php?rid=3270519&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F88212856v3941111%2F Abstract  Expressions of cell-cycle regulating proteins are altered after stroke. Cell-cycle inhibition has shown dramatic reduction in infarction after stroke. Ceramide can induce cell-cycle arrest by up-regulation of cyclin-dependent kinase (Cdk) inhibitors p21 and p27 through activation of protein phosphatase 2A (PP2A). Tricyclodecan-9-yl-xanthogenate (D609)-increased ceramide levels after transient middle cerebral artery occlusion (tMCAO) in spontaneously hypertensive rat (SHR) probably by inhibiting sphingomyelin synthase (SMS). D609 significantly reduced cerebral infarction and up-regulated Cdk inhibitor p21 and down-regulated phospho-retinoblastoma (pRb) expression after tMCAO in rat. Others have suggested bFGF-induced astrocyte proliferation is attenuated by D609 du... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3270519 Thu, 11 Feb 2010 11:41:18 +0100 3270519 http://www.medworm.com/index.php?rid=3270520&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0v32767754712630%2F Abstract  Astrogliosis, a cellular reaction with specific structural and functional characteristics, represents a remarkably homotypic response of astrocytes to all kinds of central nervous system (CNS) pathologies. Astrocytes play diverse functions in the brain, both harmful and beneficial. Mounting evidence indicates that astrogliosis is an underlying component of a diverse range of diseases and associated neuropathologies. The mechanisms that lead to astrogliosis are not fully understood, nevertheless, damaged neurons have long been reported to induce astrogliosis and astrogliosis has been used as an index for underlying neuronal damage. As the predominant source of proinflammatory factors in the CNS, microglia are readily activated under certain pathological conditions.... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3270520 Thu, 11 Feb 2010 11:41:17 +0100 3270520 http://www.medworm.com/index.php?rid=3247997&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl0v71160315g7411%2F Abstract  Excitotoxicity due to excess stimulation of glutamate receptors in neurons is accompanied by increased Ca2+ influx, stimulation of Ca2+-dependent enzymes, ATP depletion, increase in lipid peroxidation products, and loss of glutathione. These changes resemble neurochemical alterations in acute neuronal injury (stroke, spinal cord injury, and traumatic brain injury) and chronic neurodegenerative diseases such as Alzheimer’s disease. Intracerebroventricular injection of the potent glutamate analog kainate in rats results in increased cholesterol concentration in the hippocampus at short to medium time intervals, i.e., 3 days–1 week post-injection, as detected by gas chromatography–mass spectrometry in the lesioned hippocampus. This is accompanied by an ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3247997 Fri, 05 Feb 2010 18:19:26 +0100 3247997 http://www.medworm.com/index.php?rid=3241629&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq214755251ph6027%2F Abstract  Phospholipases A2 (PLA2s) are a diverse family of lipolytic enzymes which hydrolyze the acyl bond at the sn-2 position of glycerophospholipids to produce free fatty acids and lysophospholipids. These products are precursors of bioactive eicosanoids and platelet-activating factor which have been implicated in pathological states of numerous acute and chronic neurological disorders. To date, more than 27 isoforms of PLA2 have been found in the mammalian system which can be classified into four major categories: secretory PLA2, cytosolic PLA2, Ca2+-independent PLA2, and platelet-activating factor acetylhydrolases. Multiple isoforms of PLA2 are found in the mammalian spinal cord. Under physiological conditions, PLA2s are involved in diverse cellular responses, including ... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3241629 Tue, 02 Feb 2010 18:31:44 +0100 3241629 http://www.medworm.com/index.php?rid=3241630&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg3r717888345227x%2F Abstract  Stroke is a leading cause of adult disability and mortality. Diabetes is a major risk factor for stroke. Patients with diabetes have a higher incidence of stroke and a poorer prognosis after stroke. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a ligand-modulated transcriptional factor and a therapeutic target for treating type II diabetes. It is well-documented that activation of PPAR-γ can also attenuate postischemic inflammation and damage. In this review, we focus on the newly revealed anti-apoptotic actions of PPAR-γ against cerebral ischemia. PPAR-γ, by increasing superoxide dismutase/catalase and decreasing nicotinamide adenine dinucleotide phosphate oxidase levels, attenuated ischemia-induced reactive oxygen species and subsequently alle... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3241630 Tue, 02 Feb 2010 18:31:43 +0100 3241630 http://www.medworm.com/index.php?rid=3241631&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl372413553660122%2F Abstract  Sphingolipids are polar membrane lipids present as minor components in eukaryotic cell membranes. Sphingolipids are highly enriched in nervous cells, where they exert important biological functions. They deeply affect the structural and geometrical properties and the lateral order of cellular membranes, modulate the function of several membrane-associated proteins, and give rise to important intra- and extracellular lipid mediators. Sphingolipid metabolism is regulated along the differentiation and development of the nervous system, and the expression of a peculiar spatially and temporarily regulated sphingolipid pattern is essential for the maintenance of the functional integrity of the nervous system: sphingolipids in the nervous system participate to several si... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3241631 Tue, 02 Feb 2010 07:00:58 +0100 3241631 http://www.medworm.com/index.php?rid=3224130&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq0031135p5786603%2F Abstract  Huntington’s disease (HD) is a hereditary neurodegenerative disorder caused by expended CAG repeats in the Huntingtin (Htt) gene. The resultant mutant Htt (mHtt) forms aggregates in neurons and causes neuronal dysfunctions. The major characteristic of HD is the selective loss of neurons in the striatum and cortex, which leads to movement disorders, dementia, and eventual death. Expression of mHtt was also found in non-neuronal cells in the brain, suggesting non-cell-autonomous neurotoxicity in HD. As was documented in many different neurodegenerative disorders, elevated inflammatory responses are also reported in HD. To date, effective treatments for this devastating disease remain to be developed. This review focuses on the importance of glial cells and inflamm... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3224130 Wed, 27 Jan 2010 20:00:16 +0100 3224130 http://www.medworm.com/index.php?rid=3214353&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft815743276h42216%2F Abstract  Mitochondria are dynamic organelles that undergo continuous fission and fusion, which could affect all aspects of mitochondrial function. Mitochondrial dysfunction has been well documented in Alzheimer’s disease (AD). In the past few years, emerging evidence indicates that an imbalance of mitochondrial dynamics is involved in the pathogenesis of AD. In this review, we discuss in detail the abnormal mitochondrial dynamics in AD and how such abnormal dynamics may impact mitochondrial and neuronal function and contribute to the course of disease. Based on this discussion, we propose that mitochondrial dynamics could be a potential therapeutic target for AD. Content Type Journal ArticleDOI 10.1007/s12035-009-8095-7Authors Bo Su, Case Western Reserve University D... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3214353 Tue, 26 Jan 2010 07:06:55 +0100 3214353 http://www.medworm.com/index.php?rid=3154923&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F178175718553477j%2F Abstract  Alzheimer’s disease (AD) is the most common cause of dementia in the aging population. Prior work has shown that the ε4 allele of apolipoprotein E (apoE4) is a major risk factor for “sporadic” AD, which accounts for >99% of AD cases without a defined underlying mechanism. Recently, we have demonstrated that sulfatides are substantially and specifically depleted at the very early stage of AD. To identify the mechanism(s) of sulfatide loss concurrent with AD onset, we have found that: (1) sulfatides are specifically associated with apoE-associated particles in cerebrospinal fluid (CSF); (2) apoE modulates cellular sulfatide levels; and (3) the modulation of sulfatide content is apoE isoform dependent. These findings not only lead to identification of the p... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3154923 Wed, 06 Jan 2010 06:55:50 +0100 3154923 http://www.medworm.com/index.php?rid=3154922&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9476t9518074t45g%2F Abstract  Ca+2-dependent exocytosis involves vesicle docking, priming, fusion, and recycling. This process is performed and regulated by a vast number of synaptic proteins and depends on proper protein–protein and protein–lipid interactions. Double C2 domain (DOC2) is a protein family of three isoforms found while screening DNA libraries with a C2 probe. DOC2 has three domains: the Munc13-interacting domain and tandem C2s (designated C2A and C2B) connected by a short polar linker. The C2 domain binds phospholipids in a Ca2+-dependent manner. This review focuses on the ubiquitously expressed isoform DOC2B. Sequence alignment of the tandem C2 protein family in mouse revealed high homology (81%) between rabphilin-3A and DOC2B proteins. We created a structural model of DOC2B... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3154922 Wed, 06 Jan 2010 06:55:50 +0100 3154922 http://www.medworm.com/index.php?rid=3154925&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr163861133k12715%2F Abstract  Plasmalogen-selective phospholipase A2 (PlsEtn-PLA2) has been purified from pig brain using multiple column chromatographic procedure. The purified enzyme migrates as a single band on polyacrylamide. It is stimulated by Triton X-100 and inhibited by sodium deoxycholate. Purified PlsEtn-PLA2 is inhibited by iodoacetate, and this inhibition can be prevented by β-meracaptoethanol. Treatment of neuronal cell cultures with kainic acid stimulates PlsEtn-PLA2 activity in a dose-dependent manner, and this stimulation can be blocked by Ly294486, a selective kainic acid receptor antagonist. Activities of PlsEtn-PLA2 are markedly increased in plasma membrane and synaptosomal plasma membrane fraction prepared from nucleus basalis and hippocampal region of brains from Alzheimer... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3154925 Tue, 05 Jan 2010 06:51:22 +0100 3154925 http://www.medworm.com/index.php?rid=3154924&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa4820k3651u73133%2F Abstract  The majority of excitatory communication occurs at dendritic spines, and spine modifications accompany synaptic modifications under both physiological and pathological conditions. Although it is increasingly clear that spine remodeling is required for synaptic modification, the exact functions and underlying molecular mechanisms remain unclear. Here, we review recent progress on this topic and discuss the functions of spine remodeling in a broad sense to include both alterations in spine size and actin dynamics. We propose that these two aspects of actin remodeling have distinct contributions to synaptic modification. Content Type Journal ArticleDOI 10.1007/s12035-009-8093-9Authors Xiao-bin Wang, Mount Sinai School of Medicine Department of Neurology New York N... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3154924 Tue, 05 Jan 2010 06:51:22 +0100 3154924 http://www.medworm.com/index.php?rid=3077490&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Flh1242673167m681%2F Abstract  Alzheimer’s disease (AD) is a prevalent dementia-causing neurodegenerative disease. Neuronal death is closely linked to the progression of AD-associated dementia. Accumulating evidence has established that a 24-amino-acid bioactive peptide, Humanin, protects neurons from AD-related neuronal death. A series of studies using various murine AD models including familial AD gene-expressing transgenic mice have shown that Humanin is effective against AD-related neuronal dysfunction in vivo. Most recently, it has been shown that Humanin inhibits neuronal cell death and dysfunction by binding to a novel IL-6-receptor-related receptor(s) on the cell surface involving CNTFRα, WSX-1, and gp130. These findings suggest that endogenous Humanin [or a Humanin-like substance(s)... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=3077490 Tue, 08 Dec 2009 06:50:13 +0100 3077490 http://www.medworm.com/index.php?rid=2983016&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1u4043w551653119%2F Abstract  Duchenne muscular dystrophy is caused by mutations in the dystrophin gene and is characterized by progressive muscle wasting. A number of Duchenne patients also present with mental retardation. The dystrophin protein is part of the highly conserved dystrophin-associated glycoprotein complex (DGC) which accumulates at the neuromuscular junction (NMJ) and at a variety of synapses in the peripheral and central nervous systems. Many years of research into the roles of the DGC in muscle have revealed its structural function in stabilizing the sarcolemma. In addition, the DGC also acts as a scaffold for various signaling pathways. Here, we discuss recent advances in understanding DGC roles in the nervous system, gained from studies in both vertebrate and invertebrate mod... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=2983016 Mon, 09 Nov 2009 06:46:27 +0100 2983016 http://www.medworm.com/index.php?rid=2947985&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx0837n8468617155%2F Abstract  Glutamate is the predominant excitatory transmitter used by primary afferent synapses and intrinsic neurons in the spinal cord dorsal horn. Accordingly, ionotropic glutamate receptors mediate basal spinal transmission of sensory, including nociceptive, information that is relayed to supraspinal centers. However, it has become gradually more evident that these receptors are also crucially involved in short- and long-term plasticity of spinal nociceptive transmission, and that such plasticity have an important role in the pain hypersensitivity that may result from tissue or nerve injury. This review will cover recent findings on pre- and postsynaptic regulation of synaptic function by ionotropic glutamate receptors in the dorsal horn and how such mechanisms contribu... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=2947985 Fri, 30 Oct 2009 07:41:13 +0100 2947985 http://www.medworm.com/index.php?rid=2947986&cid=s_36001_25_f&fid=36001&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F277k216g245x4425%2F This article reviews those experiments that have studied drug-induced alterations in gene transcription. Ethanol has diverse effects on the amounts of messenger RNA molecules within the central nervous system. Ion channels, neuropeptides, membrane receptors, and immediate early genes represent several regulated mRNAs. The effects are selective, however, as many other specific products are not altered. Evidence for a genetic predisposition to ethanol use reinforces the importance of the genotype. Opioids, cocaine, and amphetamine also affect gene transcription. Messenger RNAs studied have included many of those demonstrated to be altered by alcohol use. Interestingly, use of any of these drugs alters the expression of immediate early genes. These genes may represent an initia... Molecular Neurobiology journals http://www.medworm.com/rss/comments.php?id=2947986 Thu, 29 Oct 2009 19:57:38 +0100 2947986