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 'NeuroMolecular Medicine' source. Sat, 20 Mar 2010 14:41:47 +0100 http://www.medworm.com/index.php?rid=3372084&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr167015t72052765%2F We examined synaptic function in the hippocampus of aged mice deficient for the Parkinson’s disease-linked protein, parkin. Surprisingly, heterozygous but not homozygous parkin-deficient mice exhibited impairments in basal excitatory synaptic strength. Similarly heterozygous mice exhibited broad deficits in paired-pulse facilitation, while homozygous parkin-deficient mice exhibited more restricted deficits. In contrast to the measurements of basal synaptic function, synaptic plasticity was not altered in aged heterozygous parkin-deficient mice, but was enhanced in aged homozygous parkin-deficient mice, due to an absence of age-related decline. These findings of differential synaptic phenotypes in heterozygous vs. homozygous parkin deficiency suggest compensatory responses to geneti... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3372084 Mon, 15 Mar 2010 18:00:02 +0100 3372084 http://www.medworm.com/index.php?rid=3191278&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F770267h602h17824%2F Abstract  Neuronal plasticity is associated with alternative splicing and epigenetic modulation. Recent evidence reveals the association of cytosine methylation with alternative splicing and splicing regulatory mechanisms. Single nucleotide polymorphisms (SNPs) are generally less frequent in conserved coding regions and probably in splice sites, compared to non-coding regions. CpG polymorphisms in coding regions and splice sites and their association with splicing regulatory elements have not been investigated till presently. We currently analyzed the CpG variability in 28 genes (361 constitutive and 105 alternative exons and the corresponding splice sites) associated with neurodegenerative diseases (ND). CpG polymorphisms in the splice sites of these genes are particularly... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3191278 Fri, 15 Jan 2010 00:47:47 +0100 3191278 http://www.medworm.com/index.php?rid=3169387&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F88422603mhwj2126%2F Abstract  The hallmark clinical symptom of early Alzheimer’s disease (AD) is episodic memory impairment. Recent functional imaging studies suggest that memory function is subserved by a set of distributed networks, which include both the medial temporal lobe (MTL) system and the set of cortical regions collectively referred to as the default network. Specific regions of the default network, in particular, the posteromedial cortices, including the precuneus and posterior cingulate, are selectively vulnerable to early amyloid deposition in AD. These regions are also thought to play a key role in both memory encoding and retrieval, and are strongly functionally connected to the MTL. Multiple functional magnetic resonance imaging (fMRI) studies during memory tasks have reveal... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3169387 Tue, 12 Jan 2010 18:22:50 +0100 3169387 http://www.medworm.com/index.php?rid=3117092&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg2n38851687n1084%2F Abstract  Patients affected by recurrent seizures frequently present increased homocysteine plasma levels in consequence of treatment with antiepileptic drugs. Homocysteine is proconvulsant and can affect the response to antiepileptic drugs. In addition, high homocysteine plasma levels represent a risk factor for cardiovascular and neurodegenerative diseases. To better define the role of increased homocysteine in epilepsy, we analyzed the effects of homocysteine pretreatment in the pilocarpine model of status epilepticus (SE), which is used to mimic temporal lobe epilepsy (TLE) in rodents. Precisely, we investigated whether a moderate hyperhomocysteinemia, unable to cause seizures, could sensitize rats to pilocarpine and cooperate in inducing brain lesions. We found that a s... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3117092 Mon, 21 Dec 2009 23:04:59 +0100 3117092 http://www.medworm.com/index.php?rid=3086955&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft643pq765436l708%2F Abstract  Manganism is a distinct medical condition from Parkinson’s disease. Manganese exposure scenarios in the last century generally have changed from the acute, high-level exposure conditions responsible for the occurrence of manganism to chronic exposure to much lower levels. Such chronic exposures may progressively extend the site of manganese deposition and toxicity from the globus pallidus to the entire area of the basal ganglia, including the substantia nigra pars compacta involved in Parkinson’s disease. The mechanisms of manganese neurotoxicity from chronic exposure to very low levels are not well understood, but promising information is based on the concept of susceptibility that may place individuals exposed to manganese at a higher risk for developing Par... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3086955 Thu, 10 Dec 2009 15:24:27 +0100 3086955 http://www.medworm.com/index.php?rid=3041836&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbk42216506084204%2F Abstract  Metal dyshomeostasis in the brain (BMD) has often been proposed as a possible cause for several neurodegenerative disorders (NDs). Nevertheless, the precise nature of the biochemical mechanisms of metal involvement in NDs is still largely unknown. Mounting evidence suggests that normal aging itself is characterized by, among other features, a significant degree of metal ion dysmetabolism in the brain. This is probably the result of a progressive deterioration of the metal regulatory systems and, at least in some cases, of life-long metal exposure and brain accumulation. Although alterations of metal metabolism do occur to some extent in normal aging, they appear to be highly enhanced under various neuropathological conditions, causing increased oxidative stress an... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3041836 Sat, 28 Nov 2009 07:06:29 +0100 3041836 http://www.medworm.com/index.php?rid=3041837&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F601qq64v8255341j%2F We describe alterations in hippocampal plasticity, which occur in both chronic stress and AD including dendritic remodeling, neurogenesis, and long-term potentiation. Finally, we outline potential roles for oxidative stress and neurotrophic factor signaling as the key determinants of the impact of chronic stress on the plasticity of neural networks and AD pathogenesis. Content Type Journal ArticleCategory Review PaperDOI 10.1007/s12017-009-8107-9Authors Sarah M. Rothman, Laboratory of Neurosciences, National Institute on Aging Intramural Research Program Baltimore MD 21224 USAMark P. Mattson, Laboratory of Neurosciences, National Institute on Aging Intramural Research Program Baltimore MD 21224 USA Journal NeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 (Sou... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3041837 Fri, 27 Nov 2009 07:07:53 +0100 3041837 http://www.medworm.com/index.php?rid=3041838&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbp17511116261u07%2F In this study, we mainly investigated the mRNA and protein expression and cellular localization of SSeCKS during chronic constriction injury (CCI). Reverse transcriptase-mediated PCR and western blot analysis revealed that SSeCKS was present in normal whole spinal cord. It gradually increased, and reached a peak at 2 weeks for its mRNA level and 7 days for its protein level after CCI. The protein expression of SSeCKS was further analyzed by immunohistochemistry. The positively stained areas for SSeCKS changed with the similar pattern to that of protein expression detected by immunoblotting analysis. Double immunofluorescence staining showed SSeCKS immunoreactivity was mostly co-localized with neurons, partly with activated astrocytes and rarely with microglia in the superfi... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3041838 Wed, 25 Nov 2009 17:03:36 +0100 3041838 http://www.medworm.com/index.php?rid=3032246&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F50451126g7181610%2F In this study, case-controlled association analysis was performed to determine if the PCNT gene is implicated in SZ. Nine SNPs were analyzed in 1,477 individuals (726 patients with SZ and 751 healthy controls). No significant difference was observed between the controls and the patients in allelic frequencies or genotypic distributions of eight SNPs. Although allelic distribution of rs11702684 was different between the two groups (P = 0.042), the difference did not reach statistical significance after permutation correction for multiple comparisons. In the haplotypic analysis, we could not find any significant association in our subjects, either. This gene may not play a major role independently in the etiology of SZ in the Japanese population. Content Type Journal Articl... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3032246 Tue, 24 Nov 2009 07:16:08 +0100 3032246 http://www.medworm.com/index.php?rid=3032245&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd26rj37218185474%2F In conclusion, we suggest that HTR2A may play an important role in the pathophysiology of the therapeutic response to SSRIs in Japanese MDD patients. However, it will be important to replicate and confirm these findings in other independent studies using large samples. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s12017-009-8105-yAuthors Taro Kishi, Fujita Health University School of Medicine Department of Psychiatry Toyoake, Aichi 470-1192 JapanReiji Yoshimura, University of Occupational and Environmental Health Department of Psychiatry Kitakyushu, Fukuoka 807-8555 JapanTsuyoshi Kitajima, Fujita Health University School of Medicine Department of Psychiatry Toyoake, Aichi 470-1192 JapanTomo Okochi, Fujita Health University School of Medicine Department of Psychiatry... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3032245 Tue, 24 Nov 2009 07:16:08 +0100 3032245 http://www.medworm.com/index.php?rid=3032247&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk398j571nr081k1t%2F Abstract  The generation of amyloid β-peptide (Aβ) by enzymatic cleavages of the β-amyloid precursor protein (APP) has been at the center of Alzheimer’s disease (AD) research. While the basic process of β- and γ-secretase-mediated generation of Aβ is text book knowledge, new aspects of Aβ and other cleavage products have emerged in recent years. Also our understanding of the enzymes involved in APP proteolysis has increased dramatically. All of these discoveries contribute to a more complete understanding of APP processing and the physiologic and pathologic roles of its secreted and intracellular protein products. Understanding APP processing is important for any therapeutic strategy aimed at reducing Aβ levels in AD. In this review, we provide a concise descripti... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3032247 Tue, 24 Nov 2009 07:16:04 +0100 3032247 http://www.medworm.com/index.php?rid=2990878&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F55681m7330r3850w%2F Abstract  A functional intracellular transport system is essential to maintain cell shape and function especially in elongated cells, e.g. neurons and lens fibre cells. Impaired intracellular transport has been suggested as a common pathological mechanism for age-related diseases characterised by protein aggregation. Here, we hypothesise that common genetic variation in the transport protein kinesin may influence the risk of Parkinson’s disease (PD), Alzheimer’s disease (AD) and age-related cataract. This case–control study involves a PD material (165 cases and 190 controls), an AD material (653 cases and 845 controls) and a cataract material (495 cases and 183 controls). Genetic variation in the kinesin light chain 1-encoding gene (KLC1) was tagged by six tag single n... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2990878 Thu, 12 Nov 2009 18:01:18 +0100 2990878 http://www.medworm.com/index.php?rid=2983018&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm4510153088t37h7%2F Abstract  Manganese (Mn) is essential for brain growth and metabolism, but in excess can be a neurotoxicant. The chemical form (species) of Mn influences its kinetics and toxicity. Significant Mn species entering the brain are the Mn2+ ion and Mn citrate which, along with Mn transferrin, enter the brain by carrier-mediated processes. Although the divalent metal transporter (DMT-1) was suggested to be a candidate for brain Mn uptake, brain Mn influx was not different in Belgrade rats, which do not express functional DMT-1, compared to controls. Brain Mn influx was not sodium dependent or dependent on ATP hydrolysis, but was reduced by mitochondrial energy inhibitors. Mn and Fe do not appear to compete for brain uptake. Brain Mn uptake appears to be mediated by a Ca uptake mec... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2983018 Mon, 09 Nov 2009 19:08:42 +0100 2983018 http://www.medworm.com/index.php?rid=2961286&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft7u8015111144374%2F Abstract  The amyloid β-peptide theory of Alzheimer’s Disease has helped to advance our understanding of the disease tremendously. A new area of research focuses on the changes in neuronal network activity that take place and may contribute to the clinical and pathological picture of Alzheimer’s Disease. An apparent symptom of altered neuronal network activity in Alzheimer’s Disease is an increased frequency in epileptic seizures that is observed both in human patients and in mouse models of Alzheimer’s Disease. A root cause for altered network activity may be amyloid β itself by its ability to alter synaptic (glutamatergic) transmission and to impair the induction of long-term potentiation. It is on this aspect of Alzheimer’s Disease research that the current i... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2961286 Tue, 03 Nov 2009 11:07:15 +0100 2961286 http://www.medworm.com/index.php?rid=2945548&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7p577j3455431510%2F Content Type Journal ArticleCategory ErratumDOI 10.1007/s12017-009-8084-zAuthors Michael Aschner, Vanderbilt University Medical Center Departments of Pediatrics and Pharmacology and the Kennedy Center for Research on Human Development 2215-B Garland Avenue, 11425 MRB IV Nashville TN 37232-0414 USAKeith M. Erikson, University of North Carolina at Greensboro Department of Nutrition Greensboro NC USAElena Herrero Hernández, Oregon Health and Science University Center for Research on Occupational and Environmental, Toxicology Portland OR USARonald Tjalkens, Colorado State University Environmental and Radiological Health Sciences Fort Collins CO USA Journal NeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 (Source: NeuroMolecular Medicine) NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2945548 Wed, 28 Oct 2009 20:36:23 +0100 2945548 http://www.medworm.com/index.php?rid=2929126&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc56l241j3401u81m%2F Abstract  The recent discovery of a number of genes involved in familial forms of Parkinson’s disease (PD) has moved the use of model genetic organisms to the frontline. One avenue holding tremendous potential to find therapies against human diseases is the use of intact living systems where complex biological processes can be examined. Despite key differences that need to be taken into account when using invertebrate models such as Drosophila, there are many advantages offered by this system. The rapid generation time and the ability to easily generate transgenic animals together with the variety of genetic tools to control temporal and spatial expression of any given gene makes the fly model a very attractive system to study human neurodegenerative disorders. In this rev... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2929126 Fri, 23 Oct 2009 18:48:12 +0100 2929126 http://www.medworm.com/index.php?rid=2929127&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu3v8310t558r3t77%2F Abstract  Phospholipases A2 (PLA2s) belong to a superfamily of enzymes responsible for hydrolyzing the sn-2 fatty acids of membrane phospholipids. These enzymes are known to play multiple roles for maintenance of membrane phospholipid homeostasis and for production of a variety of lipid mediators. Over 20 different types of PLA2s are present in the mammalian cells, and in snake and bee venom. Despite their common function in hydrolyzing fatty acids of phospholipids, they are diversely encoded by a number of genes and express proteins that are regulated by different mechanisms. Recent studies have focused on the group IV calcium-dependent cytosolic cPLA2, the group VI calcium-independent iPLA2, and the group II small molecule secretory sPLA2. In the central nervous system (CN... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2929127 Fri, 23 Oct 2009 18:48:11 +0100 2929127 http://www.medworm.com/index.php?rid=2918188&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff57n24k638421155%2F Abstract  Immunoglobulins are proteins with a highly variable antigen-binding domain and a constant region (Fc domain) that binds to a cell surface receptor (FcR). Activation of FcRs in immune cells (lymphocytes, macrophages, and mast cells) triggers effector responses including cytokine production, phagocytosis, and degranulation. In addition to their roles in normal responses to infection or tissue injury, and in immune-related diseases, FcRs are increasingly recognized for their involvement in neurological disorders. One or more FcRs are expressed in microglia, astrocytes, oligodendrocytes, and neurons. Aberrant activation of FcRs in such neural cells may contribute to the pathogenesis of major neurodegenerative conditions including Alzheimer’s disease, Parkinson’s d... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2918188 Wed, 21 Oct 2009 09:02:20 +0100 2918188 http://www.medworm.com/index.php?rid=2918189&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqk117066741l2141%2F Abstract  The vascular hypothesis of Alzheimer’s disease (AD) has brought the vascular endothelial growth factor (VEGF) into focus. The genomic region including the VEGF gene has been linked to AD and single nucleotide polymorphisms (SNPs) of the VEGF have in previous studies been associated with AD risk. To further evaluate these findings, we genotyped two SNPs in the VEGF gene (rs699947 [−2578]) and rs1570360 [−1154]) by TaqMan Allelic Discrimination in a study sample including AD patients (n = 801) and controls (n = 286). In a subgroup of the population these SNPs were analyzed in relation to APOE ε4 genotype, to cerebrospinal fluid biomarkers (T-tau, P-tau, and β42-Amyloid) as well as to neuropathological markers for AD (neurofibrillary tangles an... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2918189 Tue, 20 Oct 2009 16:30:38 +0100 2918189 http://www.medworm.com/index.php?rid=2906713&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw6w6063517423121%2F Abstract  Neurodegenerative diseases, including Alzheimer’s disease (AD), target specific and functionally connected neuronal networks, raising the possibility that neurodegeneration may spread through abnormal patterns of neural network activity. AD is associated with high levels of amyloid-β (Aβ) peptides in the brain, synaptic depression, aberrant excitatory neuronal activity, and cognitive decline. However, the relationships among these alterations and their underlying mechanisms are poorly understood. In experimental models of AD, high concentrations of pathogenic Aβ assemblies reduce glutamatergic transmission and enhance long-term depression at the synaptic level. At the network level, they cause dysrhythmias, including neuronal synchronization, epileptiform act... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2906713 Fri, 16 Oct 2009 17:44:04 +0100 2906713 http://www.medworm.com/index.php?rid=2896734&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq877022tvt7h248m%2F Abstract  Neurologic disease promoted by microbial pathogens, sterile injury, or neurodegeneration rapidly induces innate immunity in adjacent healthy tissue, which in turn contributes extensively to neurologic injury. With more recent focus on innate immune processes, it appears that necrotic, but not apoptotic, death mechanisms provoke inflammatory responses likely due to the release or production of endogenous ligands that activate resident immune cells of the central nervous system. These ligands comprise a diverse set of proteins, nucleic acids, and glycosaminoglycans, including heat shock proteins, HMGB1, RNA, DNA, hyaluronan, and heparin sulfate, that stimulate innate immune mechanisms largely through Toll-like receptors (TLRs). The blockade of interactions between e... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2896734 Wed, 14 Oct 2009 17:11:23 +0100 2896734 http://www.medworm.com/index.php?rid=2896735&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy647283x0p5422x7%2F Abstract  It has been suggested a possible role of oxidative stress and lipid peroxidation in the inflammatory processes and in the pathogenesis of multiple sclerosis. Human serum paraoxonase 1 is a polymorphic enzyme encoded by the gene PON1, located in chromosome 7q21.3, that plays a major role in the metabolism of organophosporus compounds, and in the protection against oxidative stress. Paraoxonase-1 activity has been found decreased in the plasma of multiple sclerosis patients. An association between PON1 polymorphism and the risk of multiple sclerosis has been described in Italians. To investigate the possible association between the PON1 genotype and allelic variants of the polymorphisms L55M and Q192R and the risk for multiple sclerosis in the Spanish Caucasian popul... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2896735 Tue, 13 Oct 2009 20:35:17 +0100 2896735 http://www.medworm.com/index.php?rid=2811099&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4732481u64p4718g%2F Abstract  The complement system is a pivotal component of the innate immune system which protects the host from infection and injury. Complement proteins can be induced in all cell types within the central nervous system (CNS), where the pathway seems to play similar roles in host defense. Complement activation produces the C5 cleavage fragment C5a, a potent inflammatory mediator, which recruits and activates immune cells. The primary cellular receptor for C5a, the C5a receptor (CD88), has been reported to be on all CNS cells, including neurons and glia, suggesting a functional role for C5a in the CNS. A second receptor for C5a, the C5a-like receptor 2 (C5L2), is also expressed on these cells; however, little is currently known about its potential role in the CNS. The potent... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2811099 Thu, 17 Sep 2009 23:13:06 +0100 2811099 http://www.medworm.com/index.php?rid=2811100&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk4037p60816477q0%2F Abstract  MicroRNAS (miRNAs) have been suggested to play important roles in the central nervous system during development as well as disease. miRNAs appear to be dysregulated in a number of neurodegenerative diseases, developmental disorders, and as a result of stroke. Each miRNA has the ability to regulate hundreds of messenger RNA transcripts, both by causing degradation of the mRNA and by inhibition of protein translation. Recent findings suggest that it may eventually be possible to treat some neurological disorders by restoring or inhibiting miRNAs altered by disease pathology. Both viral delivery and administration of modified oligonucleotides mimicking or inhibiting specific miRNAs have been effective in model systems. Artificial miRNAs have also been generated for t... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2811100 Thu, 17 Sep 2009 23:13:05 +0100 2811100 http://www.medworm.com/index.php?rid=2811101&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqg6h516644334050%2F Abstract  Several investigations have reported that the translin-associated factor X gene (TSNAX)/disrupted-in-schizophrenia-1 gene (DISC1) was associated with major psychiatric disorders including schizophrenia, bipolar disorder (BP), and major depressive disorder (MDD). TSNAX is located immediately upstream of DISC1, and has been shown to undergo intergenic splicing with DISC1. It thus may also be influenced by translocation. To our knowledge, there are no reported gene-based association analyses between TSNAX and mood disorders in the Japanese population. We conducted a case–control study of Japanese samples (158 bipolar patients, 314 major depressive disorder patients, and 811 controls) with three tagging SNPs in TSNAX, selected using HapMap database. In addition, we per... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2811101 Thu, 17 Sep 2009 12:14:16 +0100 2811101 http://www.medworm.com/index.php?rid=2811102&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg6441255462423h4%2F Abstract  Gliomas are the most common form of primary brain tumors and are associated with a poor clinical outcome. The molecular mechanisms that contribute to gliomagenesis have become increasingly clear in recent years, yet much remains to be learned. This is particularly true for the role of microRNAs in gliomagenesis, as an appreciation for the significance of aberrant miRNA expression in human cancer has only emerged in the last 5 years. It is now evident that microRNAs regulate a wide variety of tumorigenic processes including cellular proliferation, differentiation, angiogenesis, invasion, and apoptosis. Here we review the current state of knowledge related to the role of microRNAs in glial tumor development. This is a rapidly evolving field and it is likely tha... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2811102 Thu, 17 Sep 2009 12:14:15 +0100 2811102 http://www.medworm.com/index.php?rid=2811103&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw25kr41026752383%2F We examined herein whether SAM supplementation could affect the course of motor neuron pathology in mice-expressing mutant human SOD-1. SAM delayed disease onset by 2–3 weeks. SAM also delayed hallmarks of neurodegeneration in these mice and in ALS, including preventing loss of motor neurons, and reducing gliosis, SOD-1 aggregation, protein carbonylation, and induction of antioxidant activity. SAM did not increase survival time. These preliminary findings, using a single concentration of SAM, suggest that SAM supplementation maybe useful as part of a comprehensive therapeutic approach for ALS. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s12017-009-8089-7Authors James Suchy, University of Massachusetts Lowell Center for Cellular Neurobiology and Neurodegen... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2811103 Wed, 16 Sep 2009 18:45:41 +0100 2811103 http://www.medworm.com/index.php?rid=2811104&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F52u05v5t0nj8051j%2F Abstract  Alzheimer’s disease (AD) is characterized neuropathologically by the deposition of different forms of amyloid β-protein (Aβ) including variable amounts of soluble species that correlate with severity of dementia. The extent of synaptic loss in the brain provides the best morphological correlate of cognitive impairment in clinical AD. Animal research on the pathophysiology of AD has therefore focussed on how soluble Aβ disrupts synaptic mechanisms in vulnerable brain regions such as the hippocampus. Synapic plasticity in the form of persistent activity-dependent increases or decreases in synaptic strength provide a neurophysiological substrate for hippocampal-dependent learning and memory. Acute treatment with human-derived or chemically prepared soluble Aβ t... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2811104 Wed, 16 Sep 2009 18:45:39 +0100 2811104 http://www.medworm.com/index.php?rid=2811105&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fvmk2g15777422647%2F Abstract  Over the past several decades there has been considerable progress in our basic knowledge as to the mechanisms and factors regulating Mn toxicity. The disorder known as manganism is associated with the preferential accumulation of Mn in the globus pallidus of the basal ganglia which is generally considered to be the major and initial site of injury. Because the area of the CNS comprising the basal ganglia is very complex and dependent on the precise function and balance of several neurotransmitters, it is not surprising that symptoms of manganism often overlap with that of Parkinson’s disease. The fact that neurological symptoms and onset of Mn toxicity are quite broad and can vary unpredictably probably reflects specific genetic variance of the physiological an... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2811105 Wed, 16 Sep 2009 18:45:38 +0100 2811105 http://www.medworm.com/index.php?rid=2697688&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw115k32006325077%2F Abstract  Fragile X syndrome (FXS), the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that can regulate the translation of specific mRNAs. It is known to regulate synaptic development through the regulation of local protein synthesis in synapses. MicroRNAs (miRNAs) are a class of small noncoding RNAs involved in almost every biological process. They exhibit spatiotemporal expression during brain development, and some miRNAs play important roles in neural development. A growing body of evidence now implicates the miRNA pathway in the molecular pathogenesis of FXS. Here we review the current state of knowledge about the microRNA pathway in neural development and... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2697688 Tue, 11 Aug 2009 00:10:20 +0100 2697688 http://www.medworm.com/index.php?rid=2686397&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft768623726656290%2F Abstract  β-site amyloid precursor protein cleaving enzyme (BACE1) is the rate-limiting enzyme for production of beta-amyloid peptides (Aβ), which are proposed to drive the pathological changes found in Alzheimer’s disease (AD). Reticulon 3 (RTN3) is a negative modulator of BACE1 (β-secretase) proteolytic activity, while peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) positively regulates BACE1 expression. The present study investigated whether there was any association between genetic variation in RTN3 and PPIL2, and either risk for AD, or levels of platelet β-secretase activity, in a large Northern Irish case-control sample. Four hundred and sixty-nine patients with a diagnosis of probable AD (NINCDS-ADRDA criteria) and 347 control individuals (MMSE >&n... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2686397 Sun, 09 Aug 2009 07:26:12 +0100 2686397 http://www.medworm.com/index.php?rid=2686398&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fjr2h2xw124928266%2F Abstract  The most recent literature on the interaction between α-synuclein in its several aggregation states and metal ions is discussed. This analysis shows two major types of interactions. Binding sites are present in the C-terminal region, and similar, low affinity (in the millimolar range) is exhibited toward many different metal ions, including copper and iron. A more complex scenario emerges for these latter metal ions, which are also able to coordinate with high affinity (in the micromolar range) to the N-terminal region of α-synuclein. Moreover, these redox-active metal ions may induce chemical modifications on the protein in vitro and in the reducing intracellular environment, and these modifications might be relevant for the aggregation properties of α-synucle... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2686398 Sun, 09 Aug 2009 07:26:11 +0100 2686398 http://www.medworm.com/index.php?rid=2680239&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy3l72687065443v6%2F Abstract  The purpose of this review is to highlight recent advances in the neuropathology associated with Mn exposures. We commence with a discussion on occupational manganism and clinical aspects of the disorder. This is followed by novel considerations on Mn transport (see also chapter by Yokel, this volume), advancing new hypotheses on the involvement of several transporters in Mn entry into the brain. This is followed by a brief description of the effects of Mn on neurotransmitter systems that are putative modulators of dopamine (DA) biology (the primary target of Mn neurotoxicity), as well as its effects on mitochondrial dysfunction and disruption of cellular energy metabolism. Next, we discuss inflammatory activation of glia in neuronal injury and how disruption of s... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2680239 Wed, 05 Aug 2009 18:43:06 +0100 2680239 http://www.medworm.com/index.php?rid=2661678&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu8113w2047623575%2F Abstract  Extant evidence indicates that individuals with bipolar disorder (BD) are differentially affected by overweight/obesity and abdominal obesity. Excess weight is associated with a more complex illness presentation, non-recovery, and recurrence. Herein, we sought to review literature describing the effects of structured individualized physical exercise on disparate neurobiological substrates implicated in the pathophysiology of BD. We conducted a PubMed search of all English-language articles published between 1966 and July 2008 with BD cross-referenced with the following search terms: exercise, neurobiology, pathophysiology, pathoetiology, brain, cognition, neuroplasticity, and neurodegeneration. Articles selected for review were based on adequacy of sample size, th... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2661678 Fri, 31 Jul 2009 18:11:16 +0100 2661678 http://www.medworm.com/index.php?rid=2643136&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv640267v7706620m%2F This study tests the hypothesis that a biallelic functional polymorphism in the promoter region of the interleukin-1 beta gene (IL1B −511C/T) affects vulnerability to geriatric depression and its manifestations, including age of onset, depression severity, and cognitive function. We genotyped the IL1B −511C/T polymorphism in 125 elderly inpatients diagnosed with major depression and 282 normal elderly controls. The depressed patients were evaluated at baseline after admission using the Hamilton Rating Scale for Depression (HAM-D) for depression severity and the Mini-Mental Status Examination (MMSE) for cognitive function; depression age of onset was evaluated by interview and medical records. We found no association between IL1B −511C/T genotypes and geriatric depression suscept... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2643136 Sat, 25 Jul 2009 08:52:42 +0100 2643136 http://www.medworm.com/index.php?rid=2604121&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F08877147327329g2%2F Abstract  Neurogenesis is defined as a process that includes the proliferation of neural stem/progenitor cells (NPCs) and the differentiation of these cells into new neurons that integrate into the existing neuronal circuitry. MicroRNAs (miRNAs) are a recently discovered class of small non-protein coding RNA molecules implicated in a wide range of diverse gene regulatory mechanisms. More and more data demonstrate that numerous miRNAs are expressed in a spatially and temporally controlled manners in the nervous system, which suggests that miRNAs have important roles in the gene regulatory networks involved in both brain development and adult neural plasticity. This review summarizes the roles of miRNAs-mediated gene regulation in the nervous system with focus on neurogenesis... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2604121 Tue, 14 Jul 2009 10:55:38 +0100 2604121 http://www.medworm.com/index.php?rid=2590072&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fnj5876565127k770%2F Abstract  Leukocytes are recruited into the cerebral microcirculation following an ischemic insult. The leukocyte–endothelial cell adhesion manifested within a few hours after ischemia (followed by reperfusion, I/R) largely reflects an infiltration of neutrophils, while other leukocyte populations appear to dominate the adhesive interactions with the vessel wall at 24 h of reperfusion. The influx of rolling and adherent leukocytes is accompanied by the recruitment of adherent platelets, which likely enhances the cytotoxic potential of the leukocytes to which they are attached. The recruitment of leukocytes and platelets in the postischemic brain is mediated by specific adhesion glycoproteins expressed by the activated blood cells and on cerebral microvascular endothe... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2590072 Mon, 06 Jul 2009 20:04:37 +0100 2590072 http://www.medworm.com/index.php?rid=2565563&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc106mm4422107481%2F In this study we have investigated the effects of neonatal estrogenic exposure upon the anterior pituitary. Both the early- and late-stage effects of exposure to a synthetic estrogenic agent, diethylstilbestrol (DES), upon pituitary gonadotroph cell function were assessed. We administered either a high dose (10 μg) or a low dose (0.1 μg) of DES to male rats during their neonatal period (P2–12). Gonadotroph function, cell number and morphology shortly after DES treatment (P18) and during adulthood (P90) were assessed. At P18 there was a significant decrease in follicle stimulating hormone (FSH) immunoreactivity in the pituitary gonadotroph cells in the high DES dose treated rats compared to control animals. No significant change in luteinizing hormone (LH) was observed ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2565563 Tue, 30 Jun 2009 15:55:26 +0100 2565563 http://www.medworm.com/index.php?rid=2558200&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk8626r53u4v08211%2F Abstract  Overproduction of the β-amyloid fragment 1–42 (Aβ1–42) is thought to contribute to synaptic dysfunction and neuronal death in Alzheimer’s disease. Mounting evidence suggests that purinergic receptors play critical roles in synaptic plasticity and neuronal survival, but the potential involvement of these receptors in Aβ1–42-induced synaptic dysfunction and neuronal death has not been addressed. Here we report that Aβ1–42 promoted accumulation of the calcium-permeable purinergic receptor P2X4 in neurons. We also report evidence that Aβ1–42 induced a caspase-3-mediated cleavage of the receptor that slowed channel closure times and prevented agonist-induced internalization of the receptor. Molecular interference to reduce the expression of P2X4 in primar... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2558200 Mon, 29 Jun 2009 08:52:39 +0100 2558200 http://www.medworm.com/index.php?rid=2549688&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx08875413k243765%2F This article reviews data on the prevalence of seizures in Alzheimer’s disease, seizure types, pathophysiology and treatment. Seizure prevalence increases with disease duration, but early-onset disease is associated with a greater risk of seizures, in part related to the frequency of presenilin-1 gene mutations in early-onset disease. Seizures are mostly of partial origin, with both complex partial and secondary generalised seizures. Seizure pathophysiology may relate to increased amyloid beta-peptide production, structural alterations in neurones related to cytoskeletal dysfunction, cerebrovascular changes, neurotransmitter dysfunction or combinations thereof. Through modification of these pathophysiological pathways, there may be possible roles for anti-epileptic drugs such as so... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2549688 Fri, 26 Jun 2009 08:15:46 +0100 2549688 http://www.medworm.com/index.php?rid=2549689&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv702ru8rxv465550%2F Abstract  It has been shown that NAD+ availability is important for neuronal survival following ischemia (Liu et al., Neuromolecular Med 11:28–42, 2009). It is proposed here that NAD+ may also control proteotoxicity by influencing both formation and catabolism of altered proteins. It is suggested that low NAD+ availability promotes synthesis of methylglyoxal (MG) which can induce formation of glycated proteins, ROS, and dysfunctional mitochondria. That glyoxalase overexpression and carnosine are both protective against MG and ischemic injury support this proposal. Recognition and elimination of altered proteins is enhanced by NAD+ through effects on stress protein expression and autophagy. Content Type Journal ArticleCategory Review PaperDOI 10.1007/s12017-009-8069-yAutho... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2549689 Thu, 25 Jun 2009 07:39:10 +0100 2549689 http://www.medworm.com/index.php?rid=2492039&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc3215723104x4g72%2F Abstract  Psychiatric illnesses are disabling disorders with poorly understood underlying pathophysiologies. However, it is becoming increasingly evident that these illnesses result from disruptions across whole cellular networks rather than any particular monoamine system. Recent evidence continues to support the hypothesis that these illnesses arise from impairments in cellular plasticity cascades, which lead to aberrant information processing in the circuits that regulate mood, cognition, and neurovegetative functions (sleep, appetite, energy, etc.). As a result, many have begun to consider future therapies that would be capable of affecting global changes in cellular plasticity to restore appropriate synaptic function and neuronal connectivity. MicroRNAs (miRNAs) are no... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2492039 Sat, 20 Jun 2009 05:50:43 +0100 2492039 http://www.medworm.com/index.php?rid=2492038&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl53601j59229n470%2F In conclusion, our findings suggest that PROKR2 may play a role in the pathophysiology of mood disorders in the Japanese population. However, because our samples were small, it will be important to replicate and confirm these findings in other independent studies using larger samples. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s12017-009-8067-0Authors Taro Kishi, Fujita Health University School of Medicine Department of Psychiatry Toyoake Aichi 470-1192 JapanTsuyoshi Kitajima, Fujita Health University School of Medicine Department of Psychiatry Toyoake Aichi 470-1192 JapanTomoko Tsunoka, Fujita Health University School of Medicine Department of Psychiatry Toyoake Aichi 470-1192 JapanTakenori Okumura, Fujita Health University School of Medicine Department of Psychi... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2492038 Sat, 20 Jun 2009 05:50:43 +0100 2492038 http://www.medworm.com/index.php?rid=2492040&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc2261p5840001372%2F Abstract  In recent years, there has been a shift in the conventional paradigms for transcriptional and translational regulation as extensive sequencing efforts have yielded new insights into the landscape of the human genome and transcriptome. Hundreds of non-coding regulatory RNA molecules called microRNAs (miRNAs) have been identified in the mammalian central nervous system (CNS) and are reported to mediate pivotal roles in many aspects of neuronal functions. Disruption of miRNA-based post-transcriptional regulation has been implicated in a range of CNS disorders as one miRNA is predicted to impact the expression of numerous downstream mRNA targets. The intricate molecular networks mediated by an miRNA form a robust mechanism for rapid and potent responses to cellular ev... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2492040 Thu, 18 Jun 2009 16:04:37 +0100 2492040 http://www.medworm.com/index.php?rid=2492041&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4l610882l1023617%2F Abstract  Multiple sclerosis (MS), which results in damage of the white matter at multiple foci, poses a far-reaching public health problem in view of the burden it imposes on the affected young and middle-aged. Some previous data suggested that roles could be played in the demyelinization of the white matter of the brain by the malfunctioning of the mitochondria and mitochondria-associated reactive oxygen species. In this context, we hypothesized that the finely tuned dynamic stability of the mitochondrial membrane potential (MMP), which is the main mirror of the functional state of the mitochondria, is essential for the intact nature of the glia cells in the brain. Setting out from this, our aim in this study was to examine how the rs10807344 and rs2270450 genetic variant... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2492041 Thu, 18 Jun 2009 16:04:36 +0100 2492041 http://www.medworm.com/index.php?rid=2492042&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu6g181j520322615%2F Abstract  Matrix metalloproteinase-9 (MMP-9) plays a role in many pathological conditions (e.g., cancer and heart disease). Recently, MMP-9 has been implicated in various aspects of brain functions (e.g., neuroplasticity and epileptogenesis) and thus, we hypothesized that MMP-9 gene may be associated with bipolar mood disorder. The study was performed on 416 patients with bipolar mood disorder, including 75 patients with bipolar II type of the illness, and in 558 healthy control persons. A functional −1562C/T polymorphism of the MMP-9 gene was genotyped in all subjects. Patients with bipolar mood disorder had significant preponderance of T allele versus C allele of 1562C/T polymorphism of the MMP-9 gene, compared to healthy control subjects. The higher frequency of T allel... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2492042 Thu, 18 Jun 2009 16:04:34 +0100 2492042 http://www.medworm.com/index.php?rid=2480464&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F665315203h107828%2F In conclusion, we could not replicate the association between seven SNPs in NOS1 and schizophrenia found in several earlier studies, using larger Japanese schizophrenia and control samples. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s12017-009-8068-zAuthors Takenori Okumura, Fujita Health University School of Medicine Department of Psychiatry Toyoake Aichi 470-1192 JapanTomo Okochi, Fujita Health University School of Medicine Department of Psychiatry Toyoake Aichi 470-1192 JapanTaro Kishi, Fujita Health University School of Medicine Department of Psychiatry Toyoake Aichi 470-1192 JapanMasashi Ikeda, Fujita Health University School of Medicine Department of Psychiatry Toyoake Aichi 470-1192 JapanTsuyoshi Kitajima, Fujita Health University School of Medicine Departme... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2480464 Wed, 10 Jun 2009 11:37:08 +0100 2480464 http://www.medworm.com/index.php?rid=2429964&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0ur435655261w071%2F In this study we will discuss these findings and their implications for our understanding of HD. Using updated bioinformatic analysis, we predict 21 new candidate microRNAs in HD. We propose future strategies for unifying large-scale transcriptional and microRNA datasets with the aim of explaining HD aetiology. By way of example, we show how available genomic datasets can be integrated to provide independent, analytical validation for dysregulation of REST and microRNA mir-124 in HD. As a consequence, gene ontology analysis indicates that HD is characterised by a broad-based depression of neural genes in the caudate and motor cortex. Thus, we propose that a combination of REST, microRNAs and possibly other non-coding RNAs profoundly affect the neuronal transcriptome in HD. Content... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2429964 Thu, 21 May 2009 06:01:19 +0100 2429964 http://www.medworm.com/index.php?rid=2429965&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp464w60470520v38%2F Abstract  microRNAs play an important role in regulating synaptic plasticity. For example, microRNAs target (and are targeted by) plasticity mediators such as CREB, MECP2, and FMRP. As well, specific microRNAs have been shown to be expressed within dendrites, where they regulate protein translation of targets mediating dendritic growth. Components of the RISC machinery have been implicated in long-term memory in Drosophila. Here, we review evidence from studies of adult mouse forebrain supporting a model wherein synaptic stimulation (above a threshold value) increases calcium within dendritic spines, activates calpain, and activates and releases dicer from the postsynaptic density. Dicer processes local pre-miRs into mature miRNAs that are incorporated into RISC complexes wi... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2429965 Thu, 21 May 2009 06:01:18 +0100 2429965 http://www.medworm.com/index.php?rid=2400795&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy745843h11w71873%2F Abstract  Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of lower motor neurons resulting in paralysis and death. Epidemiological and clinical findings suggest that a decline in athletic performance may presage the clinical onset of ALS, but this possibility has not been tested in an animal model. By placing running wheels in each mouse’s cage to measure their exercise activity, we show that presymptomatic G93A SOD1 ALS mice are more active runners (15–20 km/day) than control mice (7–9 km/day). The ALS mice then exhibit a sharp decline in daily running distance 10–20 days prior to the onset of clinical disease. Within the group of ALS mice, there were no significant correlations between cumulative lifetime running dist... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2400795 Wed, 06 May 2009 06:02:38 +0100 2400795 http://www.medworm.com/index.php?rid=2357908&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2r150r0554947614%2F Abstract  Mutations in the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) cause Charcot–Marie–Tooth type 2 (CMT2), a severe autosomal recessive form of neuropathy associated with axonal phenotypes. It has been screened in this study for the presence of mutations in the coding region of GDAP1, which maps to chromosome 8q21, in a family with CMT2. To date, 29 mutations in the GDAP1 have been reported in patients of different ethnic origins. Here, we report a novel missense mutation (c.836A>G), and two polymorphisms: a silent variant (c.102G>C), and a 5′-splice site mutation (IVS5+24C>T) in GDPA1 gene identified in a five generation Turkish family with autosomal recessive CMT2. Content Type Journal ArticleCategory Original PaperDOI 10.1007/... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2357908 Tue, 21 Apr 2009 10:49:16 +0100 2357908 http://www.medworm.com/index.php?rid=2335131&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy3t2132481622711%2F Abstract  We have previously identified activation of microglia and induction of the early growth response gene 1 (Egr1) in the retina of retinoschisin-deficient (Rs1h−/Y) mice. We hypothesized that microglial expression of Egr1 might support retinal microgliosis. To test this, Egr1 transcript levels were determined in RNAs isolated from early postnatal retinas and primary microglia from Rs1h−/Y mice and wild-type controls. Egr1 mRNA expression was strongly induced in retinoschisin-deficient retinas as well as in ex vivo isolated microglia. Increased microglial Egr1 protein expression was concordantly detected in retinal sections of Rs1h−/Y mice using immunohistochemistry. Prominent activation-dependent Egr1 mRNA and protein expression was also confirmed in murine BV-2 ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2335131 Tue, 14 Apr 2009 06:13:57 +0100 2335131 http://www.medworm.com/index.php?rid=2574681&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm1j2825736w4737p%2F Abstract  Recent studies have shown that selective serotonin reuptake inhibitors (SSRIs) have circadian properties, suggesting that the antidepressive action of SSRIs may also be attributable to circadian mechanisms. Another study reported an association between clock gene (CLOCK) and improvements in insomnia symptoms from SSRIs treatment. Therefore, we examined the association between CLOCK and the efficacy of fluvoxamine treatment in 121 patients with Japanese major depressive disorder (MDD). The MDD patients in this study had scores of 12 or higher on the 17 items of the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D). We defined a therapeutic response as a decrease of more than a 50% in baseline SIGH-D within 8 weeks, and clinical remiss... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2574681 Sun, 05 Apr 2009 13:09:59 +0100 2574681 http://www.medworm.com/index.php?rid=2311045&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm1j2825736w4737p%2F Abstract  Recent studies have shown that selective serotonin reuptake inhibitors (SSRIs) have circadian properties, suggesting that the antidepressive action of SSRIs may also be attributable to circadian mechanisms. Another study reported an association between clock gene (CLOCK) and improvements in insomnia symptoms from SSRIs treatment. Therefore, we examined the association between CLOCK and the efficacy of fluvoxamine treatment in 121 patients with Japanese major depressive disorder (MDD). The MDD patients in this study had scores of 12 or higher on the 17 items of the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D). We defined a therapeutic response as a decrease of more than a 50% in baseline SIGH-D within 8 weeks, and clinical remiss... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2311045 Sun, 05 Apr 2009 13:09:59 +0100 2311045 http://www.medworm.com/index.php?rid=2289552&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh4222615415107rr%2F In this study, we tested the efficacy of AAV-mediated local delivery of IFN-β for the treatment of retinoblastoma in preclinical models. Retinoblastoma is an ideal candidate for gene-therapy-based anti-cancer treatment because target cell transduction and, therefore, IFN-β delivery can be contained within the ocular environment, thereby minimizing systemic toxicity. We report here that retinoblastoma cell lines exhibit pleiotropic responses to IFN-β consistent with previous studies on a variety of tumor cell lines. Intravitreal injection of AAV-IFN-β resulted in efficient retinal infection and sustained IFN-β production in the eye with minimal systemic exposure. Vector spread outside of the eye was not detected. Using our orthotopic xenograft model of retinoblastoma, we found th... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2289552 Sun, 22 Mar 2009 06:08:10 +0100 2289552 http://www.medworm.com/index.php?rid=2278686&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0625895647j41t82%2F Abstract  Neurons require large amounts of energy to support their survival and function, and are therefore susceptible to excitotoxicity, a form of cell death involving bioenergetic stress that may occur in several neurological disorders including stroke and Alzheimer’s disease. Here we studied the roles of NAD+ bioenergetic state, and the NAD+-dependent enzymes SIRT1 and PARP-1, in excitotoxic neuronal death in cultured neurons and in a mouse model of focal ischemic stroke. Excitotoxic activation of NMDA receptors induced a rapid decrease of cellular NAD(P)H levels and mitochondrial membrane potential. Decreased NAD+ levels and poly (ADP-ribose) polymer (PAR) accumulation in nuclei were relatively early events (<4 h) that preceded the appearance of propidium iodi... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2278686 Sat, 14 Mar 2009 14:43:16 +0100 2278686 http://www.medworm.com/index.php?rid=2163936&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2311jvl0307h3142%2F Abstract  The high demand for molecular oxygen, the enrichment of polyunsaturated fatty acids in membrane phospholipids, and the relatively low abundance of antioxidant defense enzymes are factors rendering cells in the central nervous system (CNS) particularly vulnerable to oxidative stress. Excess production of reactive oxygen species (ROS) in the brain has been implicated as a common underlying factor for the etiology of a number of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke. While ROS are generated by enzymatic and nonenzymatic reactions in the mitochondria and cytoplasm under normal conditions, excessive production under pathological conditions is associated with activation of Ca2+-dependent enzymes including... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2163936 Wed, 04 Feb 2009 14:02:29 +0100 2163936 http://www.medworm.com/index.php?rid=2075145&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F408587p320887428%2F Abstract  In this article, we examined the performance of the voltammetric assay of caffeine using DNA immobilized onto a carbon nanotube paste electrode (DPE) and compared it with that of an ordinary carbon nanotube paste electrode (PE). Under optimal conditions, the working ranges for caffeine were from 0.1 to 12 mg l−1 (for DPE) and 30–230 mg l−1 (for PE). Detection limits (DLs) of 0.068 mg l−1 (3.50 × 10−7 M) DPE and 9.94 mg l−1 (5.12×10−5 M) PE were obtained and the relative standard deviation at the caffeine concentration of 5.0 mg l−1 was 0.064% (n = 15) DPE under optimum conditions. The sensor could be implanted in a leaf skin or animal brain cell, which can then be interfa... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2075145 Thu, 01 Jan 2009 06:48:32 +0100 2075145 http://www.medworm.com/index.php?rid=2075146&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl782vt5w26055164%2F Abstract  Suicidal behavior is a multifactorial phenomenon, with a significant genetic predisposition. To assess the contribution of genes in the 4p region to suicide risk, we genotyped 36 single nucleotide polymorphisms from a 49Mb region on the chromosome arm 4p11-16 in a total of 288 male suicide victims and 327 healthy male volunteers. The nonsynonymous variants rs1383180 in EVC gene, rs6811863 in TBC1D1 gene, rs362272 in HTT gene, and rs734312 in WFS1 gene were associated to the male completed suicide. However, only EVC polymorphism remained significant after correcting for multiple comparisons (P < .05 after 10 K permutations). The function of these genes is not clear yet. WFS1 and HTT are related to the unfolded protein response and endoplasmic reticu... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=2075146 Tue, 30 Dec 2008 07:34:50 +0100 2075146 http://www.medworm.com/index.php?rid=1961372&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8uj71v5347588352%2F Abstract  Substantial evidence indicates bioenergetic dysfunction and mitochondrial impairment contribute either directly and/or indirectly to the pathogenesis of numerous neurodegenerative disorders. Treatment paradigms aimed at ameliorating this cellular energy deficit and/or improving mitochondrial function in these neurodegenerative disorders may prove to be useful as a therapeutic intervention. Creatine is a molecule that is produced both endogenously, and acquired exogenously through diet, and is an extremely important molecule that participates in buffering intracellular energy stores. Once creatine is transported into cells, creatine kinase catalyzes the reversible transphosphorylation of creatine via ATP to enhance the phosphocreatine energy pool. Creatine kinase e... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1961372 Thu, 13 Nov 2008 15:56:03 +0100 1961372 http://www.medworm.com/index.php?rid=1906245&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fgvm73g3810117316%2F Abstract  Differential BDNF gene (BDNF) promoter use leads to protein isoforms differing by 8 or 15 N-terminal residues (BDNF1 and BDNF2) whose regulation and function are not completely understood versus the well-known 247-aa BDNF “short” form. To describe how BDNF isoform levels were regulated by chronic drug use, we measured BDNF isoform-specific mRNA levels in different human brain regions from cocaine addicts relative to age, race, and gender-matched controls. The cocaine group had threefold higher levels of exon 4-specific (BDNF Short) mRNAs in cerebellum versus controls (P < 0.01). In cortex, exon 4 and exon 1-specific BDNF mRNA levels (BDNF1) were significantly reduced in the cocaine group relative to controls (40%, P < 0.01). We also test... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1906245 Thu, 23 Oct 2008 06:03:02 +0100 1906245 http://www.medworm.com/index.php?rid=1775773&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj748x2616410r74g%2F Abstract  Parkinson’s disease (PD) features oxidative stress and accumulation of misfolded (unfolded, alternatively folded, or mutant) proteins with associated loss of dopaminergic neurons. Oxidative stress and the accumulated misfolded proteins elicit cellular responses that include an endoplasmic reticulum (ER) stress response that may protect cells against the toxic buildup of misfolded proteins. Chronic ER stress and accumulation of misfolded proteins in excessive amounts, however, overwhelm the cellular ‘quality control’ system and impair the protective mechanisms designed to promote correct folding and degrade faulty proteins, ultimately leading to organelle dysfunction and neuronal cell death. Paraquat belongs to a class of bipyridyl herbicides and triggers oxi... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1775773 Fri, 05 Sep 2008 17:31:31 +0100 1775773 http://www.medworm.com/index.php?rid=1750466&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp33l8638304k8070%2F Content Type Journal ArticleCategory ErratumDOI 10.1007/s12017-008-8050-1Authors Silvia Bolognin, University of Padova Department of Biology, Padova ‘‘Metalloproteins’’ Unit, CNR-Institute of Biomedical Technologies Via Ugo Bassi 58B 35121 Padova ItalyPaolo Zatta, University of Padova Department of Biology, Padova ‘‘Metalloproteins’’ Unit, CNR-Institute of Biomedical Technologies Via Ugo Bassi 58B 35121 Padova ItalyDenise Drago, University of Padova Department of Biology, Padova ‘‘Metalloproteins’’ Unit, CNR-Institute of Biomedical Technologies Via Ugo Bassi 58B 35121 Padova ItalyGiuseppe Tognon, University of Padova Department of Biology, Padova ‘‘Metalloproteins’’ Unit, CNR-Institute of Biomedical Technologies Via Ugo Bassi 58B 35121 Padova ItalyPier P... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1750466 Sat, 30 Aug 2008 17:21:58 +0100 1750466 http://www.medworm.com/index.php?rid=1750467&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff2t361l621091327%2F Abstract  The early stage of inflammation involves the adhesion and transmigration of leukocytes across the blood–brain barrier (BBB) to the normally sequestered central nervous system (CNS). This process is regulated by the expression of a series of adhesion molecules. One of the most well-known components is intercellular adhesion molecule-1 (ICAM-1). It was described as a ligand of the membrane-bound integrin receptors lymphocyte function-associated antigen-1 (LFA-1) and monocyte adhesion molecules-1 (Mac-1) on leukocytes, and was involved in the adhesion and transmigration of leukocytes. Studies have demonstrated the upregulation of ICAM-1 in many tissues after lipopolysaccharide (LPS) stimulation, for example. In the CNS, recent studies just focus on the relatively a... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1750467 Sat, 30 Aug 2008 17:21:56 +0100 1750467 http://www.medworm.com/index.php?rid=1723740&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa85460k343v05200%2F Abstract  As reported by some authors, clioquinol (CQ), a 8-hydroxyquinoline derivative, has produced very encouraging results in the treatment of Alzheimer’s disease (AD). Its biological effects are most likely ascribed to complexation of specific metal ions, such as copper (II) and zinc (II), critically associated with β-amyloid (Aβ) aggregation/fibrillogenesis and degeneration processes in the brain. The present study was aimed at assessing the in vitro effects of CQ on the aggregation/fibrillogenesis properties of human Aβ either alone or complexed with Cu2+ and Zn2+. Surprisingly, our data indicated that CQ promoted rather than inhibited the formation of Aβ fibrillar aggregates when added metal ions were present. To understand whether the latter effects were ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1723740 Tue, 19 Aug 2008 23:05:38 +0100 1723740 http://www.medworm.com/index.php?rid=1705036&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8555mh6500772w36%2F Abstract  Psychotic symptoms are common in Alzheimer’s disease (AD) and have a negative impact on quality of life. It is suggested that psychotic symptoms may be attributed to genetic risk factors which are revealed during neurodegeneration. CHRNA7, the gene for the α7 nicotinic acetylcholine receptor, has been associated with schizophrenia in linkage and association studies. Hence we investigated single SNPs and haplotypes in CHRNA7 in relation to AD with psychosis in a large, well-characterised and previously described cohort within the Northern Ireland population. A significant association between delusions and the T allele of rs6494223 (P = 0.014, OR = 1.63, CI = 1.22–2.17) was found. This suggests that the α7 receptor may be a suitabl... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1705036 Tue, 12 Aug 2008 07:23:20 +0100 1705036 http://www.medworm.com/index.php?rid=1552016&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe0541424851423rp%2F Abstract  β-Site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is a biological and positional candidate gene for Alzheimer’s disease (AD). BACE1 is a protease that catalyses APP cleavage at the β-secretase site. We evaluated all common and putatively functional polymorphisms in the genomic region encompassing BACE1 for an association with AD, and for functional effects on platelet β-secretase activity. Tag SNPs (n = 10) derived from phase II of the International HapMap Project, and a nonsynonymous variant, were successfully genotyped in 901 Caucasian individuals from Northern Ireland using Sequenom iPLEX and TaqMan technologies. APOE genotyping was performed by PCR-RFLP. Platelet membrane β-secretase activity was assayed in a subset of individuals (... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1552016 Thu, 26 Jun 2008 06:15:30 +0100 1552016 http://www.medworm.com/index.php?rid=1535965&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8r1310q48u375037%2F This article discusses critical issues of mitochondria causing dysfunction in aging and neurodegenerative diseases, and discusses the potential of developing mitochondrial medicine, particularly mitochondrially targeted antioxidants, to treat aging and neurodegenerative diseases. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s12017-008-8044-zAuthors P. Hemachandra Reddy, Oregon Health & Science University Neurogenetics Laboratory, Neurological Sciences Institute 505 NW 185th Avenue Beaverton OR 97006 USA Journal NeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 (Source: NeuroMolecular Medicine) NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1535965 Fri, 20 Jun 2008 05:51:03 +0100 1535965 http://www.medworm.com/index.php?rid=1509242&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq534h2gqk72k2260%2F Conclusions Our results suggest that the functional Val66Met polymorphism affects theta EEG asymmetry in parietal brain regions specifically in individuals with COMD. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s12017-008-8038-xAuthors Natalie L. Bulgin, University of Toronto Centre for Addiction and Mental Health 250 College St. Toronto ON Canada M5T 1R8John S. Strauss, University of Toronto Centre for Addiction and Mental Health 250 College St. Toronto ON Canada M5T 1R8Nicole A. King, University of Toronto Centre for Addiction and Mental Health 250 College St. Toronto ON Canada M5T 1R8Sajid A. Shaikh, University of Toronto Centre for Addiction and Mental Health 250 College St. Toronto ON Canada M5T 1R8Charles J. George, University of Pittsburgh Medical Center Wes... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1509242 Tue, 10 Jun 2008 05:49:55 +0100 1509242 http://www.medworm.com/index.php?rid=1509241&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1862131482676824%2F Abstract  The central nervous system is highly enriched in long-chain polyunsaturated fatty acid (PUFA) of the omega-6 and omega-3 series. The presence of these fatty acids as structural components of neuronal membranes influences cellular function both directly, through effects on membrane properties, and also by acting as a precursor pool for lipid-derived messengers. An adequate intake of omega-3 PUFA is essential for optimal visual function and neural development. Furthermore, there is increasing evidence that increased intake of the long-chain omega-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may confer benefits in a variety of psychiatric and neurological disorders, and in particular neurodegenerative conditions. However, the mechanisms underly... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1509241 Tue, 10 Jun 2008 05:49:55 +0100 1509241 http://www.medworm.com/index.php?rid=1509243&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fgk0v530683j85648%2F Abstract  The Roman poet Horace was among the first to recognize that when “clogged with yesterday’s excess, the body drags the mind down with it.” Although considerable attention has been paid in neuroscience to the enhancement of neuronal function by wheel running and caloric restriction, far less is known about the other side of this issue. What are the consequences of unhealthy habits to central nervous system function? Prolonged exposure to excessive caloric intake impairs neuronal function and also contributes to obesity and other risk factors for diabetes. Diabetes, a disease characterized by reduced sensitivity to glucose and insulin, is also associated with deficits in brain structure and function. In contrast, enhancement of somatic metabolism by wheel runni... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1509243 Tue, 10 Jun 2008 05:49:54 +0100 1509243 http://www.medworm.com/index.php?rid=1509244&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8021671057017581%2F Abstract  P-glycoprotein (P-gp), which is coded by the MDR1 gene, in the brain capillary endothelial cell limits the entry of many drugs including antipsychotics into the brain. The aim of this study is to examine whether a functional polymorphism, a C to T substitution at position 3435 in exon 26 of the MDR1 gene, is associated with susceptibility to polydipsia–hyponatremia in schizophrenia (SCZ) in a Japanese case–control sample. It has been reported that individuals homozygous for this polymorphism had significantly lower MDR1 expression levels and dysfunction of MDR1 (PNAS 97:3473–3478, 2000). Furthermore, the brain entry of risperidone and 9-hydroxyrisperidone has been shown to be greatly limited by P-gp (Int J Neuropsychopharmacol 7:415–419, 2004). In order to o... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1509244 Tue, 10 Jun 2008 05:49:53 +0100 1509244 http://www.medworm.com/index.php?rid=1509246&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy5458178834j015m%2F Abstract  Amyloid plaques are composed primarily of amyloid-beta (Aβ) peptides derived from proteolytic cleavage of amyloid precursor protein (APP) and are considered to play a pivotal role in Alzheimer’s disease (AD) pathogenesis. Presently, AD is diagnosed after the onset of clinical manifestations. With the arrival of novel therapeutic agents for treatment of AD, there is an urgent need for biomarkers to detect early stages of AD. Measurement of plasma Aβ has been suggested as an inexpensive and non-invasive tool to diagnose AD and to monitor Aβ modifying therapies. However, the majority of cross-sectional studies on plasma Aβ levels in humans have not shown differences between individuals with AD compared to controls. Similarly, cross-sectional studies of mouse pl... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1509246 Tue, 10 Jun 2008 05:49:52 +0100 1509246 http://www.medworm.com/index.php?rid=1509245&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0234784862203488%2F Abstract  Compelling evidence from epidemiological studies suggests beneficial roles of dietary phytochemicals in protecting against chronic disorders such as cancer, and inflammatory and cardiovascular diseases. Emerging findings suggest that several dietary phytochemicals also benefit the nervous system and, when consumed regularly, may reduce the risk of disorders such as Alzheimer’s and Parkinson’s diseases. The evidence supporting health benefits of vegetables and fruits provide a rationale for identification of the specific phytochemicals responsible, and for investigation of their molecular and cellular mechanisms of action. One general mechanism of action of phytochemicals that is emerging from recent studies is that they activate adaptive cellular stress respon... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1509245 Tue, 10 Jun 2008 05:49:52 +0100 1509245 http://www.medworm.com/index.php?rid=1509247&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp2m2717301m33721%2F Conclusion These results, combined with previous findings indicating alterations in the frequency for the HNMT Thr105Ile polymorphism in patients with PD, suggest that alterations of histamine homeostasis in the SNC are associated with the risk of movement disorders. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s12017-008-8040-3Authors Maria C. Ledesma, Medical School, University of Extremadura Department of Pharmacology & Psychiatry Badajoz SpainElena García-Martín, School of Biological Sciences, University of Extremadura Department of Biochemistry and Molecular Biology Avda. de Elvas s/n 06071 Badajoz SpainHortensia Alonso-Navarro, Príncipe de Asturias Hospital, University of Alcalá de Henares Department of Medicine-Neurology Madrid SpainCarmen Martínez, Medi... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1509247 Tue, 10 Jun 2008 05:49:50 +0100 1509247 http://www.medworm.com/index.php?rid=1500404&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Flp1159671050744x%2F Abstract  Exercise that engages the cardiovascular system has a myriad of effects on the body; however, we usually do not give much consideration to the benefits it may have for our minds. An increasing body of evidence suggests that exercise can have some remarkable effects on the brain. In this article, we will introduce how exercise can impact the capacity for neurons in the brain to communicate with one another. To properly convey this information, we will first briefly introduce the field of synaptic plasticity and then examine how the introduction of exercise to the experimental setting can actually alter the basic properties of synaptic plasticity in the brain. Next, we will examine some of the candidate physiological processes that might underlay these alterations. ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1500404 Fri, 06 Jun 2008 05:53:07 +0100 1500404 http://www.medworm.com/index.php?rid=1488830&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F967gng0774084623%2F Abstract  Integrin β4, one of the heterodimeric receptors, is expressed predominantly on epithelial cells. It is concentrated at the basement membrane zone, where it localizes to specialized adhesion structures called hemidesmosomes. In addition to its adhesive functions, novel insights have emerged regarding the specific roles of integrin β4 in their attachment to extracellular matrix and in their signal transduction pathways within the central nervous system (CNS) and peripheral nervous system in the past few years. It has been reported that integrin β4 is expressed in several kinds of neural cells including astrocyte, Schwann cells, neurons, and neural stem cells. In the mean while, it is expressed by some Schwann cells in the peripheral nervous system and mediated th... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1488830 Sat, 31 May 2008 06:52:51 +0100 1488830 http://www.medworm.com/index.php?rid=1488829&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh373q56730m1427l%2F Abstract  Stress-related mood deterioration and affective disorders, such as depression, are among the leading causes of disease burden throughout the world, and are associated with severe medical consequences and mortality. Research has shown the involvement of dysfunctional brain serotonin (5-HT) biochemistry as a vulnerable biological factor in the onset of mood disturbances. Since the production of brain serotonin is limited by the availability of its plasma dietary amino acid precursor tryptophan, different foods and dietary amino acids that influence tryptophan availability are thought to alter affective behavior by changing brain 5-HT synthesis. Most dietary manipulation studies, however, reveal only modest affective changes, and note that these particularly occur in... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1488829 Sat, 31 May 2008 06:52:51 +0100 1488829 http://www.medworm.com/index.php?rid=1303518&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fjg58j24124uw4718%2F Abstract  Cardiovascular diseases including hypertension, myocardial infarction, stroke, and heart failure continue to account for the majority of deaths in the developed world. Whilst the incidence of these clinical disorders does increase with age, outcomes in affected patients tend to be disproportionately adverse with advancing years. In this context it is important to understand the various compensatory processes which become activated in cardiovascular disease. In particular, the autonomic nervous system is known to play a key pathogenic role in the cause and response to many of these conditions. The normal aging process is accompanied by a complex series of changes in the autonomic control of the cardiovascular system, favoring heightened cardiac sympathetic tone wit... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1303518 Thu, 13 Mar 2008 07:01:17 +0100 1303518 http://www.medworm.com/index.php?rid=1261871&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd71p3266786g7275%2F Abstract  Exercise can prevent the development of stress-related mood disorders, such as depression and anxiety. The underlying neurobiological mechanisms of this effect, however, remain unknown. Recently, researchers have used animal models to begin to elucidate the potential mechanisms underlying the protective effects of physical activity. Using the behavioral consequences of uncontrollable stress or “learned helplessness” as an animal analog of depression- and anxiety-like behaviors in rats, we are investigating factors that could be important for the antidepressant and anxiolytic properties of exercise (i.e., wheel running). The current review focuses on the following: (1) the effect of exercise on the behavioral consequences of uncontrollable stress and the implic... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1261871 Tue, 26 Feb 2008 15:33:42 +0100 1261871 http://www.medworm.com/index.php?rid=1250531&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F869q486238540128%2F Abstract  Physical exercise exerts a wide range of benefits on an organism’s overall health and well-being. Exercise contributes positively toward an individual’s healthy weight, muscle strength, immune system, and cardiovascular health. Indeed, exercise has been demonstrated to reduce life-threatening conditions such as high blood pressure, heart disease, obesity, and diabetes. Of particular interest to this review, exercise has also been shown to be neuroprotective in both the central and peripheral nervous systems. Naturally, such findings apply broadly to the study of neurodegenerative disease with numerous reports demonstrating that exercise has beneficial effects on disease progression. One of the most devastating neurodegenerative diseases is amyotrophic lateral ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1250531 Wed, 20 Feb 2008 16:07:12 +0100 1250531 http://www.medworm.com/index.php?rid=1250527&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F07x8jp6315p270n2%2F Abstract  The discovery that exercise regulates adult hippocampal neurogenesis, that is, the production of new neurons in the adult brain, was surprising news and changed quite fundamentally our view on how physical activity affects the brain. The everyday experience that not all athletes are necessarily smarter than more sedentary fellows and the scientific insight that adult hippocampal neurogenesis is actually a process that ranges on a very small scale raised important questions on the relevance of this finding. We propose that the exercise-related regulation of adult hippocampal neurogenesis is a qualitative rather than a quantitative event and that it is a particularly prominent and suggestive example of activity-dependent cellular plasticity. For rodents, the animals... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1250527 Wed, 20 Feb 2008 16:07:10 +0100 1250527 http://www.medworm.com/index.php?rid=1250530&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy151875715540800%2F Abstract  Research in humans and animals has shown that exercise improves mood and cognition. Physical activity also causes a robust increase in neurogenesis in the dentate gyrus of the hippocampus, a brain area important for learning and memory. The positive correlation between running and neurogenesis has raised the hypothesis that the new hippocampal neurons may mediate, in part, improved learning associated with exercise. The present review gives an overview of research pertaining to exercise-induced cell genesis, its possible relevance to memory function and the cellular mechanisms that may be involved in this process. Content Type Journal ArticleCategory Review PaperDOI 10.1007/s12017-008-8028-zAuthors Henriette van Praag, GRC/NIA/NIH Section of Neuroplasticity and... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1250530 Wed, 20 Feb 2008 16:07:08 +0100 1250530 http://www.medworm.com/index.php?rid=1250529&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp665171685786172%2F Abstract  Physical exercise has long been recognized as highly beneficial for brain and body health. The molecular mechanisms responsible for translation of exercise stimuli in the brain have claimed attention due to mounting evidence for the neuroprotective actions of the exercise and its positive effects in preventing both ageing and neurodegenerative disease. These molecular mediators are currently under investigation with new tools able to yield deep insights into the neurobiology of exercise. In the present work we focus on the evidence pertaining to the mediation of exercise effects by insulin-like growth factor 1 (IGF1), as recent reports suggest that this growth factor shows brain area-specific, temporal rank-sensitive, and behavioural task-dependent features in res... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1250529 Wed, 20 Feb 2008 16:07:08 +0100 1250529 http://www.medworm.com/index.php?rid=1250528&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff5p1275155l48402%2F Conclusion    While aging and neurodegeneration in PD and AD are associated with accumulation of COX− cells and mtDNA deletions, the pathology of MS is not. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s12017-008-8025-2Authors Andrei Blokhin, VA Medical Center, Research (151) Syracuse NY USATamara Vyshkina, VA Medical Center, Research (151) Syracuse NY USASamuel Komoly, Medical University of Pecs Pecs HungaryBernadette Kalman, VA Medical Center, Research (151) Syracuse NY USA Journal NeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 (Source: NeuroMolecular Medicine) NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1250528 Wed, 20 Feb 2008 16:07:08 +0100 1250528 http://www.medworm.com/index.php?rid=1237146&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa2852t323411q347%2F Abstract  Habitual exercise increases plasticity in a variety of neurotransmitter systems. The current review focuses on the effects of habitual physical activity on monoamine dopamine (DA) neurotransmission and the potential implication of these changes to exercise-induced fatigue. Although it is clear that peripheral adaptations in muscle and energy substrate utilization contribute to this effect, more recently it has been suggested that central nervous system pathways “upstream” of the motor cortex, which initiate activation of skeletal muscles, are also important. The contribution of the brain to exercise-induced fatigue has been termed “central fatigue.” Given the well-defined role of DA in the initiation of movement, it is likely that adaptations in DA systems... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1237146 Fri, 15 Feb 2008 17:58:04 +0100 1237146 http://www.medworm.com/index.php?rid=1234886&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr2x5577137220453%2F Abstract  Stress exerts complex effects on the brain and periphery, dependent on the temporal profile and intensity of the stressor. The consequences of a stressful event can also be determined by other characteristics of the stressor, such as whether it is predictable and controllable. While the traditional view has focused primarily on the negative effects of stress on a variety of somatic systems, emerging data support the idea that certain forms of stress can enhance cellular function. Here we review the current literature on the hypothalamic-pituitary-adrenal (HPA) axis regulation by wheel running, a voluntary and controllable stressor with a distinct temporal profile. While running indeed activates a number of systems related to the stress response, other mechanisms e... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1234886 Thu, 14 Feb 2008 16:08:18 +0100 1234886 http://www.medworm.com/index.php?rid=1232124&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp46p211416g87jqm%2F Content Type Journal ArticleCategory ErratumDOI 10.1007/s12017-008-8024-3Authors Amy Chan, University of Massachusetts Lowell Center for Cellular Neurobiology & Neurodegeneration Research Lowell MA 01854 USAThomas B. Shea, University of Massachusetts Lowell Center for Cellular Neurobiology & Neurodegeneration Research Lowell MA 01854 USA Journal NeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 (Source: NeuroMolecular Medicine) NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1232124 Wed, 13 Feb 2008 16:09:52 +0100 1232124 http://www.medworm.com/index.php?rid=1198212&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv160081l25q57031%2F Abstract  Mutations in DJ-1 cause inherited Parkinson’s disease (PD) in several families. The normal function of DJ-1 is unknown, but mice lacking DJ-1 exhibit a deficit in dopaminergic signaling in the striatum. Since the hippocampus contains relatively high levels of DJ-1, and PD patients are often cognitively impaired, we evaluated the effects of DJ-1 deficiency on the plasticity of hippocampal CA1 synapses. LTP was slightly impaired and LTD was abolished in DJ-1−/− mice, whereas DJ-1+/− mice exhibited no alterations in synaptic plasticity. The dopamine receptor D2/3 agonist quinpirole rescued LTD in DJ-1−/− mice, suggesting a role for impaired dopaminergic signaling in the hippocampal LTD deficit. Content Type Journal ArticleCategory Original PaperDOI 10.1... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1198212 Sat, 02 Feb 2008 16:47:17 +0100 1198212 http://www.medworm.com/index.php?rid=1183089&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F03735278hw220525%2F Abstract  The metabolic syndrome is characterized by the clustering of various common metabolic abnormalities in an individual and it is associated with increased risk for the development of type 2 diabetes and cardiovascular diseases. Its prevalence in the general population is approximately 25%. Central fat accumulation and insulin resistance are considered as the common denominators of the abnormalities of the metabolic syndrome. Subjects with metabolic syndrome have autonomic nervous system dysfunction characterized by predominance of the sympathetic nervous system in many organs, i.e. heart, kidneys, vasculature, adipose tissue, and muscles. Sympathetic nervous system activation in metabolic syndrome is detected as increased heart rate and blood pressure, diminished he... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1183089 Sat, 26 Jan 2008 16:31:22 +0100 1183089 http://www.medworm.com/index.php?rid=1156106&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr4884968p801w8n5%2F Abstract  Epidemiological studies of the Guamanian variants of amyotrophic lateral sclerosis (ALS) and parkinsonism, amyotrophic lateral sclerosis–parkinsonism dementia complex (ALS–PDC), have shown a positive correlation between consumption of washed cycad seed flour and disease occurrence. Previous in vivo studies by our group have shown that the same seed flour induces ALS and PDC phenotypes in out bred adult male mice. In vitro studies using isolated cycad compounds have also demonstrated that several of these are neurotoxic, specifically, a number of water insoluble phytosterol glucosides of which β-sitosterol β-d-glucoside (BSSG) forms the largest fraction. BSSG is neurotoxic to motor neurons and other neuronal populations in culture. The present study ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1156106 Tue, 15 Jan 2008 16:12:47 +0100 1156106 http://www.medworm.com/index.php?rid=1131291&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh1127g504q2h1060%2F Abstract  During development, neurotrophic factors are known to play important roles in regulating the survival of neurons in the autonomic nervous system (ANS) and the formation of their synaptic connectivity with their peripheral targets in the cardiovascular, digestive, and other organ systems. Emerging findings suggest that neurotrophic factors may also affect the functionality of the ANS during adult life and may, in part, mediate the effects of environmental factors such as exercise and dietary energy intake on ANS neurons and target cells. In this article, we describe the evidence that ANS neurons express receptors for multiple neurotrophic factors, and data suggesting that activation of those receptors can modify plasticity in the ANS. Neurotrophic factors that may ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1131291 Thu, 03 Jan 2008 16:51:22 +0100 1131291 http://www.medworm.com/index.php?rid=1017953&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr11568834187048w%2F Abstract  The sympathetic nervous system (SNS) and pain interact on many levels of the neuraxis. In healthy subjects, activation of the SNS in the brain usually suppresses pain mainly by descending inhibition of nociceptive transmission in the spinal cord. Furthermore, some experimental data even suggest that the SNS might control peripheral inflammation and nociceptive activation. However, even subtle changes in pathophysiology can dramatically change the effect of SNS on pain, and vice versa. In the periphery, inflammation or nociceptive activation is enhanced, spinal descending inhibition is reversed to spinal facilitation, and finally the awareness of all these changes will induce anxiety, which furthermore amplifies pain perception, affects pain behavior, and depresses... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1017953 Thu, 08 Nov 2007 16:11:22 +0100 1017953 http://www.medworm.com/index.php?rid=1012545&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8368305518617738%2F Abstract  Familial dysautonomia (FD) is a sensory and autonomic neuropathy that affects the development and survival of sensory, sympathetic, and some parasympathetic neurons. It is autosomally inherited and occurs almost exclusively among individuals of Ashkenazi Jewish descent. The pathological and clinical manisfestations of FD have been extensively studied and therapeutic modalities have, until recently, focused primarily on addressing the symptoms experienced by those with this fatal disorder. The primary FD-causing mutation is an intronic nucleotide substitution that alters the splicing of the IKBKAP-derived transcript. Recent efforts have resulted in the development of new therapeutic modalities that facilitate the increased production of the correctly spliced transcr... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1012545 Tue, 06 Nov 2007 15:53:14 +0100 1012545 http://www.medworm.com/index.php?rid=1012546&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F029512742xx1642t%2F Abstract  A dominant paradigm in neurological disease research is that the primary etiological factors for diseases such as Alzheimer’s (AD), Parkinson’s (PD), and amyotrophic lateral sclerosis (ALS) are genetic. Opposed to this perspective are the clear observations from epidemiology that purely genetic casual factors account for a relatively small fraction of all cases. Many who support a genetic etiology for neurological disease take the view that while the percentages may be relatively small, these numbers will rise in the future with the inevitable discoveries of additional genetic mutations. The follow up argument is that even if the last is not true, the events triggered by the aberrant genes identified so far will be shown to impact the same neuronal cell death ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1012546 Tue, 06 Nov 2007 15:53:13 +0100 1012546 http://www.medworm.com/index.php?rid=1012547&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy55232l51185153t%2F Conclusion    These results, combined with previous findings indicating alterations in histamine levels in patients with PD, suggest that alterations of histamine homeostasis in the SNC are associated with the risk for PD. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s12017-007-8017-7Authors José A. G. Agúndez, University of Extremadura Department of Pharmacology & Psychiatry, Medical School Badajoz SpainAntonio Luengo, University Hospital La Princesa Service of Neurology Madrid SpainOscar Herráez, University of Extremadura Department of Pharmacology & Psychiatry, Medical School Badajoz SpainCarmen Martínez, University of Extremadura Department of Pharmacology & Psychiatry, Medical School Badajoz SpainHortensia Alonso-Navarro, Príncipe de As... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=1012547 Tue, 06 Nov 2007 15:53:05 +0100 1012547 http://www.medworm.com/index.php?rid=992151&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl12988721r47j823%2F Abstract  Neuroinflammation is observed in neurodegenerative diseases like Alzheimer’s disease (AD). However, a little is known about the mechanisms of neural-immune interactions. The involvement of peripheral T-cell function in AD is still far from clear, though it plays an important role in immunotherapy. The aim of this study was to determine peripheral T-cell reactivity in AD patients and in an AD mouse model. Mitogenic activation via ligation of the T-cell receptor (TCR) with PHA-L was measured in T lymphocytes from AD patients and Thy1(APP751SL) � HMG(PS1M146L)-transgenic mice (APP � PS1). In order to uncover failures in TCR signaling, the TCR was also bypassed by PMA and ionomycin treatment. All patients were sporadic late onset cases and the... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=992151 Fri, 26 Oct 2007 14:28:08 +0100 992151 http://www.medworm.com/index.php?rid=956303&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F960tu76503501442%2F In this study, we examined how the kinesin light-chain 1 (KLC1) G56836C (rs8702) single nucleotide polymorphism (SNP) in intron 13 affects the occurrence of MS. This genetic variant was found to be associated with cognitive disturbances and neurodegeneration, and it was presumed to affect the kinesin function. Kinesin serves as a main cytoskeleton motor protein by carrying mitochondria and the molecular apparatus of myelin basic protein synthesis. The present association analysis of this genetic variant was performed in 102 relapsing-remitting MS patients and in 207 neuroimaging alteration-free controls. The KLC1 56836CC variant proved to exert a significant protective effect on the occurrence of MS (2.0% vs. 9.7%, P < 0.02; crude OR: 0.19, 95% CI: 0.04–0.82, P &l... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=956303 Sat, 13 Oct 2007 17:27:54 +0100 956303 http://www.medworm.com/index.php?rid=903890&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F26622q351q0001gt%2F Abstract  There is evidence to suggest a role for immune dysfunction in the pathogenesis of Alzheimer’s disease, and it has previously been shown that blood plasma levels of the protein complement factor H, a member of the alternative complement pathway, was specifically elevated in people with late-onset Alzheimer’s disease. We have genotyped the common complement factor H Y402H polymorphism in a large case–control cohort to investigate association with late-onset Alzheimer’s disease susceptibility and find no evidence that this SNP is associated with disease risk. However, it remains possible that another variant in this gene may modify susceptibility for late-onset Alzheimer’s disease. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s12017-007-... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=903890 Sun, 23 Sep 2007 17:53:58 +0100 903890 http://www.medworm.com/index.php?rid=880398&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F06mh177p78351180%2F Abstract  Eating disorders (ED) are a group of important psychiatric disorders that affect young men and women, and can have serious consequences. Among all ED, anorexia nervosa (AN) is the most typical but also the most severe. The pathogenesis of AN is multifactorial and a great variety of cognitive deficits may contribute to its pathogenesis. The present study is aimed to measure NO and peroxynitrite production, iNOS and nNOS expression by Western immunoblot after incubation of AN lipoproteins at different times with human astrocytoma cells. The AN-HDL treated cells showed an increased production of NO at 3 h versus control-HDL treated cells and a decreased production at 24 h. Regarding LDL, a significant increase of NO production was obtained both at 3 and 24&... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=880398 Mon, 17 Sep 2007 17:42:22 +0100 880398 http://www.medworm.com/index.php?rid=846021&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2r3562wn2w354981%2F Abstract  It is increasingly recognized that life-style factors, such as physical exercise or diet influence brain health. In the present work we analyzed the effect of a western-style diet (“cafeteria diet”) on the entrance to the brain of circulating IGF-1, a neuroprotective agent that has been related to different neurodegenerative diseases. Rats under a cafeteria diet showed reduced passage of systemic IGF-1 across the choroid plexus, a main site of IGF-1 entrance into the brain through the cerebrospinal fluid. Furthermore, the IGF-1 receptor at the choroid plexus of rats fed with a cafeteria diet showed enhanced sensitivity toward IGF-1 while receptor levels remained unchanged. Examination of possible mechanisms underlying reduced entrance of systemic IGF-1 to the ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=846021 Wed, 05 Sep 2007 07:18:14 +0100 846021 http://www.medworm.com/index.php?rid=833750&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4044865786811v65%2F Abstract  One of the main hallmarks of Alzheimer’s disease (AD) is the brain deposition of senile plaques made up of toxic amyloid β-peptide (Aβ), which is derived from a larger protein called the β-amyloid precursor protein (APP). Both APP processing and cholinesterase activity are affected in the AD brain, but, yet, cholinesterase inhibitors (ChEI) remain the primary Food and Drug Administration approved drugs for AD within the United States. Herein, we evaluated the effects of two clinically relevant drugs on the APP pathway, which is presumably involved in AD pathogenesis. Specifically, we compared the actions of the classical ChEI physostigmine (PHY) and its analog phenserine (PHE) on neuronal cell viability, on IC50 and on levels of different amyloid proteins. Int... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=833750 Thu, 30 Aug 2007 07:51:02 +0100 833750 http://www.medworm.com/index.php?rid=833753&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fuu0k4082452t0848%2F Abstract  The use of RNA interference (RNAi) to suppress the expression of genes has drastically improved the ability to examine gene function and is now being considered as a therapeutic approach for many diseases including genetic forms of neurodegenerative disease. Recently, research has focused on RNAi for the treatment of Huntington’s and other polyglutamine diseases. In this work we explored the efficacy and specificity of short hairpin RNAs to target human huntingtin mRNA. We found two sequences that are specific for, and efficiently suppress human huntingtin mRNA. Mouse cell lines that stably harbored human short hairpin RNA constructs specifically inhibited the expression of human huntingtin supplied by transfected expression plasmids. However, these same constru... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=833753 Thu, 30 Aug 2007 07:51:01 +0100 833753 http://www.medworm.com/index.php?rid=833752&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb20041m8276r6308%2F Abstract  Tuberous sclerosis (TS) is an autosomal dominant disease associated with the formation of usually benign tumors or hamartomas. The disease is connected with upregulation of mammalian target of rapamycin, central regulator of protein translation, which is usually regarded to be activated by Akt kinase. Here, we show for the first time that in all four brain lesions and one angiomyolipoma from TS patients both extracellular signal-regulated kinase (Erk) and p90 ribosomal S6 kinase 1 activation as well as Erk-dependent phosphorylation of p70 ribosomal S6 kinase 1 are markedly elevated whereas Akt, participating in the classical pathway of mammalian target of rapamycin activation is not always activated. Erk activation is also present in TS-derived cell lines. Importa... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=833752 Thu, 30 Aug 2007 07:51:01 +0100 833752 http://www.medworm.com/index.php?rid=833751&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk8322252413x61l4%2F Abstract  Temporal lobe epilepsy (TLE) is often caused by a neurodegenerative brain insult that triggers epileptogenesis, and eventually results in spontaneous seizures, i.e., epilepsy. Understanding the mechanisms of cell death is a key for designing new drug therapies for preventing the neurodegeneration associated with TLE. Here, we investigated the expression of caspase 2, a protein involved in programmed cell death, during the course of epilepsy. We investigated caspase 2 expression in hippocampal samples derived from patients operated on for drug refractory TLE. To understand the evolution of altered-caspase 2 expression during the epileptic process, we also examined caspase 2 expression and activity in the rat hippocampus after status epilepticus-induced acute damage... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=833751 Thu, 30 Aug 2007 07:51:01 +0100 833751 http://www.medworm.com/index.php?rid=833748&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F368w08241133r18k%2F Abstract  The identification of the genetic variants underpinning bipolar disorder (BPD) has been impeded by a complex pattern of inheritance characterized by genetic and phenotypic heterogeneity, genetic epistasis, and gene-environment interactions. In this paper two strategies were used to ameliorate these confounding factors. A unique South African sample including 190 individuals of the relatively, reproductively isolated Afrikaner population was assessed with a battery of neuropsychological tests in an attempt to identify a BPD-associated quantitative trait or endophenotype. BPD individuals performed significantly worse than their unaffected relatives on visual and verbal memory tasks, a finding congruent with the literature. A focused linkage and family-based associat... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=833748 Thu, 30 Aug 2007 07:51:01 +0100 833748 http://www.medworm.com/index.php?rid=833755&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa7270r70j4016182%2F Abstract  To identify low-penetrance genes related to sporadic essential tremor (ET) at the CYP2Clocus, located in chromosome 10 q23.33. Leukocytary DNA from 200 ET patients and a control group of 300 unrelated healthy individuals with known CYP2C19 genotypes was studied for common CYP2C8 and CYP2C9 allelic variants by using amplification-restriction analyses. Patients with ET showed the following differences compared with healthy subjects: a 1.6-fold reduction in the frequency for CYP2C8*3 (p=0.006), a 1.35-fold reduction of CYP2C9*2 (p=0.05) and a 1.52-fold reduction in the frequency for CYP2C9*3 (p=0.07). The frequency for patients with ET carrying at least one defective allele was 1.33-fold reduced as compared with healthy subjects (p=0.002). In addition, a disruption of t... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=833755 Thu, 30 Aug 2007 07:51:00 +0100 833755 http://www.medworm.com/index.php?rid=833754&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft25042x889524254%2F Abstract  Human immunodeficiency virus-1 gp120 alters astroglial function, which compromises the function of the nearby of neuronal cells contributing to the cognitive impairment in human immunodeficiency virus-1 infection. Cyclooxygenase (COX)-2 has been involved in this process, although the intracellular pathways and second messengers involved are yet unknown. We have investigated the role of gp120-induced COX-2 in the astrocytoma human cell line U-87, and the different pathways involved in this activation. COX-2 mRNA and protein expression were detected in gp120-stimulated cells. Moreover, gp120 induces COX-2 promoter transcription. The effect of gp120 was abrogated by a neutralizing antibody against the chemokine receptor CXCR4 neutralizing antibody. Analysis of the pr... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=833754 Thu, 30 Aug 2007 07:51:00 +0100 833754 http://www.medworm.com/index.php?rid=833749&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj3t3356222337615%2F Abstract  A number of linkage studies have previously implicated the region of chromosome 13q34 in schizophrenia. Chumakov and colleagues (2002) identified a gene complex called G72 (now termed d-amino acid oxidase activator: DAOA)/G30 in this region and performed association analyses of the DAOA/G30 as well as the d-amino-acid oxidase (DAAO) gene with schizophrenia. DAAO oxidizes d-serine, a potent activator of the N-methyl-d-aspartate (NMDA) type glutamate receptor in the human brain whereas the DAOA protein is considered an activator of DAAO. The interaction of these two genes has thus been implicated in the NMDA receptor regulation pathway in schizophrenia. To date, several studies have shown a relatively consistent positive association between schizophrenia and DAOA/G30, ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=833749 Thu, 30 Aug 2007 07:51:00 +0100 833749 http://www.medworm.com/index.php?rid=815379&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp07r012581633836%2F Abstract  In addition to cognitive impairment, behavioral changes such as aggressive behavior, depression, and psychosis accompany Alzheimer’s Disease. Such symptoms may arise due to imbalances in neurotransmitters rather than overt neurodegeneration. Herein, we demonstrate that combined administration of N-acetyl cysteine (an antioxidant and glutathione precursor that protects against Abeta neurotoxicity), acetyl-l-carnitine (which raises ATP levels, protects mitochondria, and buffers Abeta neurotoxicity), and S-adenosylmethionine (which facilitates glutathione usage and maintains acetylcholine levels) enhanced or maintain cognitive function, and attenuated or prevented aggression, in mouse models of aging and neurodegeneration. Enhancement of cognitive function was rapid... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=815379 Tue, 21 Aug 2007 07:12:58 +0100 815379 http://www.medworm.com/index.php?rid=815380&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff075318j56378411%2F Abstract  The heat shock protein (Hsp) system is a cell defense mechanism constitutively expressed at the basal state and essential for cell survival in response to damaging stimuli. Apoptosis is a physiological cell death program that preserves tissue homeostasis. We investigated the intrinsic pathway of apoptosis at various stages of brain maturation in CD-1 mice, triggered by two mitochondrial proapoptotic proteins, cytochrome c and Smac/DIABLO, and the pathway’s regulation by Hsp-70. Smac/DIABLO and Hsp-70 proteins were upregulated 2-fold and 1.5–3-fold, respectively, after birth. In contrast, in the presence of cytochrome c/2′-deoxyadenosine 5′-triphosphate (dATP), caspase activity in mouse brain cell-free extracts increased 90-fold and 61-fold, at fetal and neo... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=815380 Tue, 21 Aug 2007 07:12:57 +0100 815380 http://www.medworm.com/index.php?rid=800214&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc76620q7322njxl1%2F Abstract  NMDA receptors (NMDARs) are important for the propagation of seizures. To understand the role of NR1 subunits in the propagation of seizures we knocked down the NR1 subunit by intracranial injection of antisense deoxyoligonucleotides (NR1-AS-ODNs) into the right hippocampus during a window of maximal seizure susceptibility in development. Control missense and sense ODNs followed by focal injection of NMDA (2.5–25 nmoles) into the hippocampal CA1 and sensorimotor cortex of P15 rat pups resulted in behavioral and electrographic (EEG) seizures. After NR1 knockdown, low- and high-doses produced little or no spike activity in the hippocampus and overlying sensorimotor cortex as predicted. Despite reduced activity in the hippocampal and cortical EEG, intracranial ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=800214 Tue, 14 Aug 2007 07:30:43 +0100 800214 http://www.medworm.com/index.php?rid=800213&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl35w645844xl5672%2F Abstract  Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily affects motor neurons and descending motor tracts of the CNS. We have evaluated the CNS of a murine model of familial ALS based on the over-expression of mutant human superoxide dismutase (mSOD; G93A) using magnetic resonance microscopy (MRM) and immunohistochemistry (IHC). Three-dimensional volumetric analysis was performed from 3D T2*-weighted images acquired at 17.6 T at isotropic resolutions of 40 μm. Compared to controls, mSOD mice had significant reductions in the volumes of total brain, substantia nigra, striatum, hippocampus, and internal capsule, with decreased cortical thickness in primary motor and somatosensory cortices. In the spinal cord, mSOD mice had significantl... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=800213 Tue, 14 Aug 2007 07:30:43 +0100 800213 http://www.medworm.com/index.php?rid=795903&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk20158m6401q401h%2F Abstract  Uric acid is a major antioxidant in the blood of humans that can protect cultured neurons against oxidative and metabolic insults. However, uric acid has a very low solubility which compromises its potential clinical use for neurodegenerative disorders. Here we describe the synthesis, characterization and preclinical development of neuroprotective methyl- and sulfur-containing analogs of uric acid with increased solubility. In vitro and cell culture screening identified 1,7-dimethyluric acid (mUA2) and 6,8-dithiouric acid (sUA2) as two analogs with high antioxidant and neuroprotective activities. When administered intravenously in mice, uric acid analogs mUA2 and sUA2 lessened damage to the brain and improved functional outcome in an ischemia-reperfusion mous... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795903 Fri, 10 Aug 2007 07:13:06 +0100 795903 http://www.medworm.com/index.php?rid=795904&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0m69w52717006350%2F Abstract  Degenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases are believed to be causally related to the accumulation of amyloid oligomers that exhibit a common structure and may be toxic by a common mechanism involving permeabilization of membranes. We discovered that amyloid oligomers and the pore-forming bacterial toxin, α-hemolysin (αHL), as well as human perforin from cytotoxic T lymphocytes, share a structural and functional homology at the level of their common reactivity with a conformation-dependent antibody that is specific for amyloid oligomers, A11. The αHL oligomeric pores and partially folded αHL protomer, but not the monomer αHL precursor reacts with A11 antibody. A11 antibody inhibits the hemolytic activity of αHL, i... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795904 Thu, 09 Aug 2007 12:25:07 +0100 795904 http://www.medworm.com/index.php?rid=795913&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy8475064v7k1n7m4%2F Abstract  Studies using genetic manipulations have proven invaluable in the research of neurological disorders. In the forefront of these approaches is the knockout technology that engineers a targeted gene mutation in mice resulting in inactivation of gene expression. In many cases, important roles of a particular gene in embryonic development have precluded the in vivo study of its function in the adult brain, which is usually the most relevant experimental context for the study of neurological disorders. The conditional knockout technology has provided a tool to overcome this restriction and has been used successfully to generate viable mouse models with gene inactivation patterns in certain regions or cell types of the postnatal brain. This review first describes the me... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795913 Wed, 08 Aug 2007 06:53:54 +0100 795913 http://www.medworm.com/index.php?rid=795912&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8240twu68j1w1370%2F Abstract  Amyloid β (Aβ) peptides have been shown to impair synaptic function, especially long-term synaptic plasticity, in transgenic mouse models of Alzheimer’s disease (AD) and in acute hippocampal preparations. In the transgenic mice overexpressing mutant forms of human amyloid precursor protein (APP), the deficits in hippocampal long-term potentiation (LTP) occur prior to synaptic loss and cell death, suggesting early functional changes at these synapses. Recent studies demonstrate that Aβ-induced synaptic dysfunction is linked with altered Ca2+ signaling in hippocampal neurons. While reducing Ca2+ influx through NMDA receptors, Aβ peptides elevate intracellular Ca2+ concentration by enhancing Ca2+ influx from voltage-gated Ca2+ channels or nonselective cation chan... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795912 Wed, 08 Aug 2007 06:53:54 +0100 795912 http://www.medworm.com/index.php?rid=795916&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7853214515473434%2F Abstract  Folate deprivation induces neurotoxicity that is potentiated by additional nutritional and genetic deficiencies including vitamin E and apolipoprotein E deficiency. These deficiencies collectively induce oxidative damage, cognitive impairment, and compensatory alteration in glutathione generation. Treatment with agents that regulate distinct portions of the methionine cycle, including the S-adenosyl homocysteine hydrolase inhibitor, 3-deaza adenosine, the methyl donor S-adenosyl methionine, and the antioxidant N-acetyl cysteine, provide neuroprotection against various aspects of neurotoxicity in normal and apolipoprotein E-deficient mice and in cultured neuronal cells deprived of dietary folate and vitamin E and subjected to iron overload. Here it is demonstrated t... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795916 Wed, 08 Aug 2007 06:53:53 +0100 795916 http://www.medworm.com/index.php?rid=795920&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fmw63n60081545r23%2F Abstract  Increased production of neurotoxic forms of amyloid β-peptide (Aβ) and abnormalities in neuronal calcium homeostasis play central roles in the pathogenesis of Alzheimer’s disease (AD). Notch, a membrane receptor that controls cell-fate decisions during development of the nervous system, has been linked to AD because it is a substrate for the γ-secretase enzyme activity that involves the presenilin-1 (PS1) protein in which mutations cause early-onset inherited AD. The actions of Notch can be antagonized by Numb, an evolutionarily conserved protein that exists in four isoforms that differ in two functional domains: a phosphotyrosine-binding (PTB) domain and a proline-rich region (PRR). We now report that Numb isoforms containing a short PTB domain increase the ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795920 Wed, 08 Aug 2007 06:53:52 +0100 795920 http://www.medworm.com/index.php?rid=795917&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F542n22j414u61685%2F Abstract   PSEN1 and PSEN2 encode polytopic membrane proteins, termed presenilin 1 (PS1) and presenilin 2 (PS2) that play an essential role in intramembranous (“γ-secretase”) proteolysis of selected type I membrane proteins, that include Notch1 and β-amyloid precursor protein (APP). In order to gain insights into biochemical mechanisms underlying γ-secretase processing of Notch1 and APP, we have developed a novel in vitro assay in which γ-secretase-mediated generation of S3/NICD and APP-CTFγ can be readily detected in isolated membrane fractions derived from immortalized PS1+/− mouse embryonic fibroblasts; production of the APP and Notch1 derivatives are inhibited by a highly selective and potent γ-secretase inhibitor, L-685,458, with a IC50 of ∼50 pM. In memb... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795917 Wed, 08 Aug 2007 06:53:52 +0100 795917 http://www.medworm.com/index.php?rid=795908&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv051981k606j5440%2F In this report, the pathological importance of a segment of ataxin-1 previously shown to be important for protein-protein interactions was examined. While the absence of a 122 amino acid segment from the protein-protein interaction region of ataxin-1 did not effect the initiation of disease, its absence substantially suppressed the progression of disease in SCA1 transgenic mice. Thus, these data suggest that this region of ataxin-1 has a role in disease progression. Furthermore, these results provide evidence that ataxin-1-induced disease initiation and disease progression involve distinct molecular events. Content TypeJournal Article JournalNeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 Journal VolumeVolume 1 Journal IssueVolume 1, Number 1 / February... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795908 Wed, 08 Aug 2007 06:53:52 +0100 795908 http://www.medworm.com/index.php?rid=795919&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb851g838705l004x%2F Abstract  Consumption of cycad seed products (Cycas circinalis) is one of the strongest epidemiological links to the Guamian neurological disorder amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC), however, the putative toxin which causes neurodegeneration has never been identified definitively. To reexamine this issue, 6–7-mo-old, male CD-1 mice were assessed for motor and cognitive behaviours during and following feeding with pellets made from washed cycad flour. Cycad-fed animals showed early evidence of progressive motor and cognitive dysfunctions. Neurodegeneration measured using TUNEL and caspase-3 labeling was found in neocortex, various hippocampal fields, substantia nigra, olfactory bulb, and spinal cord. In vitro studies using rat neocortex ha... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795919 Wed, 08 Aug 2007 06:53:51 +0100 795919 http://www.medworm.com/index.php?rid=795918&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk62h4pkv52085277%2F We describe the cloning and characterization of a rat single transmembrane protein that is homologous to the common neurotrophin receptor p75NTR in its death domain and the transmembrane region but dissimilar outside these regions. We have dubbed this protein PLAIDD, for p75-like apoptosis-inducing death domain protein. PLAIDD messenger RNA, which is ubiquitously distributed, is highly expressed in the embryo, but downregulated in adult tissues. Alternative splicing within the extracellular region of PLAIDD generates four RNA species, but only two of them are translated, PLAIDD_L and PLAIDD_S (long and short isoforms, respectively). While the amino acid sequence of the intracellular region of PLAIDD displays 41% identity with the intracellular region of p75NTR, the extracellular regio... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795918 Wed, 08 Aug 2007 06:53:51 +0100 795918 http://www.medworm.com/index.php?rid=795911&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3246148282k5g242%2F Content TypeJournal Article JournalNeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 Journal VolumeVolume 2 Journal IssueVolume 2, Number 1 / August, 2002 (Source: NeuroMolecular Medicine) NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795911 Wed, 08 Aug 2007 06:53:51 +0100 795911 http://www.medworm.com/index.php?rid=795921&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9h6034546q373811%2F Abstract  Signals between neurons are transduced primarily by receptors, and second messenger and kinase cascades, located in pre- and postsynaptic terminals. Such synaptic signaling pathways include those activated by neurotransmitters, cytokines, neurotrophic factors, and cell-adhesion molecules. Many of these signaling systems are also localized in the growth cones of axons and dendrites, where they control pathfinding and synaptogenesis during development. Although it has been known for decades that such signaling pathways can affect the survival of neurons, by promoting or preventing a form of programmed cell death known as apoptosis, we have discovered that apoptotic biochemical cascades can exert local actions on the functions and structural dynamics of growth cones ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795921 Wed, 08 Aug 2007 06:53:50 +0100 795921 http://www.medworm.com/index.php?rid=795906&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Faj47295787343096%2F Abstract  Inflammatory processes involving glial cell activation are associated with amyloid plaques and neurofibrillary tangles, the cardinal neuropathological lesions in the brains of Alzheimer’s disease (AD) patients, However, it is unclear whether these inflammatory processes occur as a response to neuronal degeneration or might represent more seminal events in the disease process. Some cases of AD are caused by mutations in presenilin-1 (PS1), and it has been shown that PS1 mutations perturb neuronal calcium homeostasis, promote increased production of amyloid β-peptide (Aβ), and render neurons vulnerable to synaptic dysfunction, excitotoxicity, and apoptosis. Although glial cells express PS1, it is not known if PS1 mutations alter glial cell functions. We now repo... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795906 Wed, 08 Aug 2007 06:53:50 +0100 795906 http://www.medworm.com/index.php?rid=795922&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0808x938p163n185%2F This article focuses on α-synuclein’s role in normal and pathological axonal and presynaptic functions and its relationship to Parkinson’s disease. It is not possible to mention all the contributions to aspects of this area. Readers interested in α-synuclein’s relation to aggregation, Lewy lesions, and pathological modifications are referred to the many reviews (see Goldberg and Lansbury 2000; Galvin 2001a; Goedert 2001). Content TypeJournal Article JournalNeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 Journal VolumeVolume 2 Journal IssueVolume 2, Number 2 / October, 2002 (Source: NeuroMolecular Medicine) NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795922 Wed, 08 Aug 2007 06:53:49 +0100 795922 http://www.medworm.com/index.php?rid=795915&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy163827040h78148%2F Abstract  Pathological alterations in the microtubule-associated protein (MAP) tau are well-established in a number of neurodegenerative disorders, including Alzheimer’s Disease (AD), frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), and others. Tau protein and in some cases, neurofilament subunits exhibit abnormal phosphorylation on specific serine and threonine residues in these diseases. A large body of biochemical, genetic, and cell biological evidence implicate two major serine-threonine protein kinases, glycogen synthase kinase 3 (GSK-3) and cyclin-dependent kinase 5 (CDK5) as major kinases responsible for both normal and pathological phosphorylation of tau protein in vivo. What remains unclear is whether tau phosphorylation and/or neurofibrillary... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795915 Wed, 08 Aug 2007 06:53:49 +0100 795915 http://www.medworm.com/index.php?rid=795907&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg01wwn21w0134615%2F Abstract  The microtubule (MT)-associated protein (MAP) tau in neurons has been implicated as a significant factor in the axonal growth, development of neuronal polarity, and the maintenance of MT dynamics. Tau is localized to the axon, and is known to promote MT assembly and to stabilize axonal MTs. These functions of tau are primarily regulated by the activities of protein kinases and phosphatases. In Alzheimer’s disease and other neurodegenerative disorders, abundant filamentous tau inclusions are found to be major neuropathological characteristics of these diseases. Both somato-dendritic and axonal tau lesions appear to be closely associated with axonal disruption. Furthermore, recent discoveries of pathogenic mutations on the tau gene suggest that abnormalities of ta... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795907 Wed, 08 Aug 2007 06:53:49 +0100 795907 http://www.medworm.com/index.php?rid=795910&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn08910182xm31k8w%2F Abstract  G protein-coupled receptors (GPCRs) currently represent pharmaceutical targets for numerous medicinal compounds that are used to treat conditions ranging from blood pressure dysregulation to depression to pain, demonstrating the wide range of functions mediated by this receptor family. GPCR activation is determined not only by the initiation of signaling cascades but also by regulatory mechanisms that control the extent and duration of their signals. The balance of activation and desensitization dictate the ultimate physiological response to both endogenous and exogenous receptor stimuli. Therefore, these mechanisms may play a particularly relevant role during chronic exposure to agonists such as in conditions when drugs are abused. Two major classes of drugs of a... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795910 Wed, 08 Aug 2007 06:53:48 +0100 795910 http://www.medworm.com/index.php?rid=795909&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe271l7q349785635%2F Abstract  Drug addiction is a complex disorder that has a large spectrum of causes. Vulnerability to addiction has been shown in twin studies to have a robust genetic component. This genetic basis for addiction has general and specific components for each drug abused. Although many genes have been implicated in drug addiction, only a handful have either been replicated to have an association or to have an identified functional mechanism related to specific effects of abused drugs. A few selected genetic variants that currently look promising for the study of alcohol, opiate, and cocaine addiction are discussed in this article. Content TypeJournal Article JournalNeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 Journal VolumeVolume 5 Journal Issu... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795909 Wed, 08 Aug 2007 06:53:48 +0100 795909 http://www.medworm.com/index.php?rid=795905&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp78834186741m086%2F Abstract  As in other cells, neurons use adenosine triphosphate (ATP) as an energy source to drive biochemical processes involved in various cell functions, and produce reactive oxygen species (ROS) as “by products” of oxidative phosphorylation. However, the electrical excitability and structural and synaptic complexity of neurons present unusual demands upon cellular systems that produce or respond to ATP and ROS. Mitochondria in axons and presynaptic terminals provide sources of ATP to drive the ion pumps that are concentrated in these structures to rapidly restore ion gradients following depolarization and neurotransmitter release. Mitochondria may also play important roles in the regulation of synaptic function because of their ability to regulate calcium levels and... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795905 Wed, 08 Aug 2007 06:53:48 +0100 795905 http://www.medworm.com/index.php?rid=795914&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fdq35684qv6326nx6%2F Abstract  Bipolar disorder (BPD) and schizophrenia (SZ) may have some common susceptibility genes, despite that current nosology separates them into nonoverlapping categories. The evidence for shared genetic factors includes epidemiologic characteristics, family studies, and overlap in confirmed linkages of BPD and/or SZ. Review of these data indicates that there are five genomic regions that may represent shared genetic susceptibility of BPD and SZ. As the genes underlying these confirmed linkages are identified, the current nosology must be changed to reflect the new knowledge concerning the shared etiologies of BPD and SZ. Content TypeJournal Article JournalNeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 Journal VolumeVolume 5 Journal Issue... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=795914 Wed, 08 Aug 2007 06:53:47 +0100 795914