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. Wed, 08 Feb 2012 20:43:30 +0100 http://www.medworm.com/index.php?rid=5639532&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0366m01476453h40%2F Abstract  Recent functional neuroimaging studies have investigated brain activity patterns during sleep in humans, beyond the conventionally defined sleep stages. These works have characterized the neural activations related to the major brain oscillations of sleep, that is, spindles and slow waves during non-rapid-eye-movement sleep and ponto-geniculo-occipital waves during rapid-eye-movement sleep. These phasic events have been found associated with increases of brain activity in specific neural networks, which identify structures involved in the generation of sleep oscillations. Most importantly, these results confirm that, even during the deepest stages of sleep, neuronal network activities are sustained and organized by spontaneous brain oscillations of sleep. The unde... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5639532 Tue, 24 Jan 2012 18:14:42 +0100 5639532 http://www.medworm.com/index.php?rid=5611194&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp84j370611210717%2F Abstract  The concept of ‘salvageble penumbra’ has prompted both scientists and physicians to explore various neuroprotective approaches that could be beneficial during stroke therapy. Unfortunately, most of them have proved ineffective in targeting multiple cellular death cascades incited within the ischemic penumbra. Hypothermia has been shown to be capable of addressing this problem to some extent. Although many studies have shown that hypothermia targets several cellular processes, its effects on innate immune receptor-mediated apoptotic death still remain unclear. Moreover, whether inhibiting the signaling of innate immune receptors like complement anaphylatoxin C5a receptor (CD88) plays a role in this hypothermic neuroprotection still need to be deciphered. Using v... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5611194 Tue, 17 Jan 2012 07:10:00 +0100 5611194 http://www.medworm.com/index.php?rid=5516365&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2301t35512436325%2F Abstract  Significant advancements have been made over the past three decades to better understand the disease entity of obstructive sleep apnea and the mechanisms by which this prevalent disorder imparts injury. Once considered a disorder of reversible sleepiness and insignificant arterial oxygen desaturations because of their intermittency, obstructive sleep apnea is now considered an independent risk factor for cardiovascular morbidity and mortality and an important contributor to neurocognitive impairment and neural injury as well as metabolic dysfunction. The rapidly fluctuating oxygen patterns are now believed to be central to oxidative injury in the brain and peripheral organs. Recent studies in both humans with sleep apnea and animal models of the disorder have incr... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5516365 Wed, 14 Dec 2011 16:30:43 +0100 5516365 http://www.medworm.com/index.php?rid=5488582&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq841x03715841426%2F Abstract  A large number of molecular pathways have been implicated in the degeneration of axotomized motoneurons. We previously have demonstrated substantial differences in the survival rate of axotomized motoneurons across different rat strains. Identification of genetic differences underlying such naturally occurring strain differences is a powerful approach, also known as forward genetics, to gain knowledge of mechanisms relevant for complex diseases, like injury-induced neurodegeneration. Overlapping congenic rat strains were used to fine map a gene region on rat chromosome eight previously shown to regulate motoneuron survival after ventral root avulsion. The smallest genetic fragment, R5, contains 35 genes and displays a highly significant regulatory effect on motone... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5488582 Wed, 07 Dec 2011 12:54:55 +0100 5488582 http://www.medworm.com/index.php?rid=5365490&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F631q7m1646h448v0%2F Abstract  The α-synuclein gene (SNCA) plays a major role in the aetiology of Lewy body disease (LBD) including Parkinson’s disease (PD). Point mutations and genetic alterations causing elevated gene expression are causally linked to familial PD. To what extent epigenetic changes play a role in the regulation of α-synuclein expression and may contribute to the aetiology of sporadic LBD is a matter of debate. We analysed the methylation state of the promoter region and a CpG-rich region of intron 1 of α-synuclein in several brain regions in sporadic LBD and controls using 454 GS-FLX-based high-resolution bisulphite sequencing. Our results indicate that there are significant differences in the level of methylation between different brain areas. The overall methylation leve... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5365490 Mon, 31 Oct 2011 16:58:54 +0100 5365490 http://www.medworm.com/index.php?rid=5365491&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu8826303641513rg%2F In this study, we investigated the effects of EGCG on cerebral function and morphology following TBI. Six-week-old male Wistar rats that had access to normal drinking water, or water containing 0.1% (w/v) EGCG ad libitum, received TBI with a pneumatic controlled injury device at 10 weeks of age. Immunohistochemistry and lipid peroxidation studies revealed that at 1, 3 and 7 days post-TBI, the number of 8-hydroxy-2′-deoxyguanosine-, 4-hydroxy-2-nonenal- and single-stranded DNA (ssDNA)-positive cells, and the levels of malondialdehyde (MDA) around the damaged area after TBI, significantly decreased in the EGCG treatment group compared with the water group (P < 0.05). Most ssDNA-positive cells in the water group co-localized with neuronal cells. However, in the E... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5365491 Fri, 28 Oct 2011 17:16:38 +0100 5365491 http://www.medworm.com/index.php?rid=5316915&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu0744k87371010k6%2F In this study, a proteomic approach was used to characterize the biomolecular disturbances that accompany neurobehavioral and neuropathological changes associated with combined exposure to PB and PER. Mice acutely exposed to PB and PER over 10 days showed an increase in anxiety-like behavior, psychomotor problems and delayed cognitive impairment compared to control mice that received vehicle only. Proteomic analysis showed changes in proteins associated with lipid metabolism and molecular transport in the brains of GW agent-exposed mice compared to controls. Proteins associated with the endocrine and immune systems were also altered, and dysfunction of these systems is a prominent feature of GWI. The presence of astrogliosis in the GW agent-exposed mice compared to control mice... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5316915 Mon, 10 Oct 2011 15:02:33 +0100 5316915 http://www.medworm.com/index.php?rid=5316916&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe1266763p8255376%2F Abstract  The recently described therapeutic benefits of the hemodialysate actovegin on neuropathic symptoms in diabetic patients with symptomatic polyneuropathy suggest a neuroprotective activity of the drug. To elucidate the possible cellular mechanism of the pharmacological effects of actovegin, we investigated its effects on cultured primary rat neurons in vitro. Primary neurons were cultured for up to 10 days in the presence of increasing doses of actovegin (0.3–1,000 mg/l). Total cell number, dendrite length and the number of excitatory synapses, i.e., the amount of the synaptic V-Glut1 protein, were measured by immunocytochemistry followed by fluorescence microscopy. The apoptotic level in neurons after induction of apoptosis by amyloid peptide Aβ25–35 ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5316916 Sat, 08 Oct 2011 15:43:59 +0100 5316916 http://www.medworm.com/index.php?rid=5306057&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fdx8l1541p5461476%2F This study focuses on changes in iron, iron-regulating proteins and RNA expression of iron metabolism genes. Three groups of samples were used: WML, normal areas from lesional WM [NAWM (L)] as disease control and normal WM from control brains [NAWM(C)]. Ferric iron staining was undertaken using known Perl’s reaction. Immunohistochemistry (IHC) of white matter for ceruloplasmin (Cp), haemochromatosis (HFE) and transferrin receptor (TfR) was done. Cellular localization of HFE and Cp was performed using dual-antibody IHC. Whole-genome RNA was extracted from WML, NAWM (L) and NAWM(C), and QPCR for HFE, TF, TfR, ceruloplasmin, ferritin and ferroportin was performed. Ferric iron staining shows increased diffuse iron staining among WML, followed by NAWM (L) and the least group being NAWM(... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5306057 Fri, 07 Oct 2011 05:45:48 +0100 5306057 http://www.medworm.com/index.php?rid=5287521&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv5u8p287751614t6%2F In this study, we analyzed the relationship between microglial activation and dopaminergic neurodegeneration to examine the possibility that neuroinflammation may induce dopaminergic neuronal loss in the nigrostriatal system. Chronic dichlorvos exposure causes microglial activation including induction of NADPH oxidase and a selective loss of dopaminergic neurons in rat. Microglial marker expression was increased at transcription as well as translational levels in the substantia nigra (SN) and corpus striatum (CS) of rats exposed to dichlorvos. Activated microglia were seen in SN and CS of dichlorvos-treated animals but were rarely observed in controls. Immunostaining revealed lesser number of TH-positive neurons and higher number of microglia in SN and CS regions after dichlorvos tre... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5287521 Mon, 03 Oct 2011 05:38:30 +0100 5287521 http://www.medworm.com/index.php?rid=5287522&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F619605g8w0666337%2F In conclusion, the renalase gene polymorphism was associated with hypertension in type 2 diabetes patients. The most interesting result is a strong association of the rs10887800 polymorphism with stroke in patients with and without diabetes. The G allele of this polymorphism might thus be useful in identifying diabetes patients at increased risk of stroke. Content Type Journal ArticleCategory Original PaperPages 1-7DOI 10.1007/s12017-011-8158-6Authors Monika Buraczynska, Laboratory for DNA Analysis and Molecular Diagnostics, Department of Nephrology, Medical University of Lublin, Dr K. Jaczewskiego 8, 20-954 Lublin, PolandPawel Zukowski, Laboratory for DNA Analysis and Molecular Diagnostics, Department of Nephrology, Medical University of Lublin, Dr K. Jaczewskiego 8, 20-954 Lubl... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5287522 Sun, 02 Oct 2011 05:47:56 +0100 5287522 http://www.medworm.com/index.php?rid=5287523&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn6714502722m1058%2F This study examined whether genetic variants in the brain-derived neurotrophic factor (BDNF) gene may be associated with body weight change after AAP treatment. The study included 481 schizophrenic patients treated with clozapine (n = 266), olanzapine (n = 79), or risperidone (n = 136) for an average of 49.2 ± 28.2 months. Three common single-nucleotide polymorphisms (SNPs) of the BDNF gene were chosen as tagging SNPs. In single-marker-based analysis, the BDNF rs11030101-T homozygous genotype was found to be associated with significantly increased body weight gain (P = 0.037). The BDNF Val66Met (rs6265) polymorphism was not found to be associated with body weight gain. Haplotype analysis further showed that the rs11030101-T-allel... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5287523 Thu, 29 Sep 2011 06:07:04 +0100 5287523 http://www.medworm.com/index.php?rid=5211288&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F726977242115j670%2F Abstract  Oxidative stress has been proposed to be an important factor in the pathogenesis of Alzheimer’s disease (AD) and contributed to β-amyloid (Aβ) generation. Interaction between oxidative stress and neuro-inflammation leads to Aβ generation. AD is associated with an increase in blood–brain barrier (BBB) permeability due to tight junction involvement. Oxidative stress decreases the expression of low-density lipoprotein receptor-related protein 1 and up-regulates receptor for advanced glycation end products in BBB and increases the BBB permeability, which could potentially lead to increased deposition of Aβ within AD brain. Apoptosis takes place in the pathogenesis of AD, and oxidative stress contributes to apoptosis through both extrinsic pathway and intrinsic ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5211288 Thu, 08 Sep 2011 05:54:55 +0100 5211288 http://www.medworm.com/index.php?rid=5211289&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa106m441kx578675%2F Abstract  Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system where it plays several pivotal roles in synaptic plasticity and neuronal survival. As a consequence, BDNF became a key target in the physiopathology of several neurological and psychiatric diseases. Recent studies have reported altered levels of BDNF in the circulation, i.e. serum or plasma, of patients with Alzheimer’s disease (AD), and low BDNF levels in the CSF as predictor of future cognitive decline in healthy older subjects. Altered BDNF circulating levels have also been reported in other neurodegenerative and psychiatric disorders, hampering its use as a specific biomarker for AD. Therefore, BDNF seems to be an unspecific biomarker of neurops... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5211289 Tue, 06 Sep 2011 08:54:31 +0100 5211289 http://www.medworm.com/index.php?rid=5133728&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F50t61u938j354581%2F Abstract  Ataxia telangiectasia (AT) is a genomic instability syndrome characterised, among others, by progressive cerebellar degeneration, oculocutaneous telangiectases, immunodeficiency, elevated serum alpha-phetoprotein level, chromosomal breakage, hypersensitivity to ionising radiation and increased cancer risk. This autosomal recessive disorder is caused by mutations in the ataxia telangiectasia mutated (ATM) gene coding for serine/threonine protein kinase with a crucial role in response to DNA double-strand breaks. We characterised genotype and phenotype of 12 Slavic AT patients from 11 families. Mutation analysis included sequencing of the entire coding sequence, adjacent intron regions, 3′UTR and 5′UTR of the ATM gene and multiplex ligation-dependent probe amplif... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5133728 Thu, 11 Aug 2011 06:56:21 +0100 5133728 http://www.medworm.com/index.php?rid=5133729&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl2246v44534863nl%2F This study suggests that the ACE I/D polymorphism does not have any genetic association with global or specific cognitive domain in aged men without dementia. Content Type Journal ArticlePages 1-5DOI 10.1007/s12017-011-8153-yAuthors Mu-En Liu, Department of Psychiatry, Kaohsiung Veterans General Hospital Pingtung Branch, Pingtung, TaiwanShih-Jen Tsai, Department of Psychiatry, Taipei Veteran General Hospital, Taipei, TaiwanTi Lu, Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, TaiwanCheng-Jee Hong, Department of Psychiatry, Taipei Veteran General Hospital, Taipei, TaiwanMing-Chao Chen, Department of Psychiatry, Kaohsiung Kai-Suan Psychiatric Hospital, Kaohsiung, TaiwanShoa-Lin Lin, Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, T... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5133729 Thu, 11 Aug 2011 06:56:19 +0100 5133729 http://www.medworm.com/index.php?rid=5031919&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj048x038l17mgx2n%2F Abstract  Amyloid-β plays a causative role in Alzheimer’s disease. Occlusal disharmony causes chronic psychological stress, and psychological stress increases amyloid-β accumulation. The purpose of the present study was to investigate whether occlusal disharmony-induced psychological stress affects the accumulation of amyloid-β and its related gene expressions in the rat hippocampus. Eight-week-old male Wistar rats (n = 18) were divided into three groups of six rats each: (1) a control group that received no treatment for 8 weeks; (2) an occlusal disharmony group that underwent cutoff maxillary molar cusps for 8 weeks; and (3) a recovered group that underwent cutoff maxillary molar cusps for 4 weeks followed by recovery for 4 weeks. Occlusa... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5031919 Wed, 13 Jul 2011 06:14:20 +0100 5031919 http://www.medworm.com/index.php?rid=4987566&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbt234w3043183247%2F Abstract  Cyclin H regulates cell cycle transitions; it always forms trimeric cyclin-dependent protein kinases (CDK)-activating kinase (CAK) complex with CDK7 and MAT1 that phosphorylates a threonine residue in the CDK2 T loop region. However, neither the expression nor function of cyclin H in the central nervous system (CNS) injury is still clear. Therefore, we studied cyclin H in a rat spinal cord contusion model. Injury markedly increased cyclin H protein expression throughout the thoracic spinal cord but did not increase CDK7. However, double immunofluorescent staining for proliferating cell nuclear antigen (PCNA) and cell markers revealed increases of cyclin H and CDK2 in proliferating microglia and astrocytes, and the co-immunoprecipitation studies shown that the asso... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=4987566 Tue, 28 Jun 2011 06:02:01 +0100 4987566 http://www.medworm.com/index.php?rid=4971635&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj7v341g318144546%2F Abstract  Stroke is a common multifactorial disease, and the third leading cause of death worldwide, which results in serious long-term mental and physical disability among survivors. The role of affected triglyceride metabolism in the development of ischemic stroke is under extensive investigations. Here, we examined three SNPs, rs12130333 located within the ANGPTL3 locus; rs16996148 residing at the CILP2 gene locus; and rs17321515 at the TRIB1 locus, which were originally reported in association with decreased triglyceride levels; therefore, we investigated their possible protective effect against the development of ischemic stroke. A total of 459 Caucasian stroke patients, stratified as large-vessel, small-vessel, and mixed stroke groups, and 168 control subjects were ge... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=4971635 Tue, 21 Jun 2011 18:34:07 +0100 4971635 http://www.medworm.com/index.php?rid=4939885&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh122t4q788g42716%2F Abstract  Preclinical evaluation of drugs for neurological disorders is usually performed on overfed rodents, without consideration of how metabolic state might affect drug efficacy. Using a widely employed mouse model of focal ischemic stroke, we found that that the NMDA receptor antagonist dizocilpine (MK-801) reduces brain damage and improves functional outcome in mice on the usual ad libitum diet, but exhibits little or no therapeutic efficacy in mice maintained on an energy-restricted diet. Thus, NMDA receptor activation plays a central role in the mechanism by which a high dietary energy intake exacerbates ischemic brain injury. These findings suggest that inclusion of subjects with a wide range of energy intakes in clinical trials for stroke may mask a drug benefit i... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=4939885 Fri, 10 Jun 2011 06:38:52 +0100 4939885 http://www.medworm.com/index.php?rid=4896822&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fwx62q215w822663k%2F In this study, we evaluated the relationships between plasma homocysteine levels and genetic risk factors for hyperhomocysteinemia, i.e., the presence of gene variants for methylenetetrahydrofolate reductase (MTHFR) and endothelial nitric oxide synthase (eNOS) in patients with cognitive impairment. Genotyping for MTHFR C677T and eNOS 894G > T polymorphisms was carried out in 69 patients with probable diagnosis of AD and anamnestic mild cognitive impairment, matched for age and gender with 69 healthy volunteers. Patients with MTHFR TT677 genotype showed higher plasma Hcy levels than controls, even after adjustment for folate levels (P < 0.05). Moreover, Hcy plasma levels were higher in cases than controls for any given eNOS genotype. In particular, the presenc... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=4896822 Mon, 23 May 2011 17:08:14 +0100 4896822 http://www.medworm.com/index.php?rid=4856373&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa53081p465t1k37r%2F Abstract  A recent editorial entitled “State of Aggregation” (Nat. Neurosci. 2011; 14:399) described the importance of establishing the structural state of pathogenic protein aggregates (Aβ, α-synuclein, huntingtin, etc.) in studies of neurodegenerative disorders. While this is a laudable goal, it is based on the assumption that the neurotoxicity depends upon a specific tertiary structure of the protein aggregates. Here, I describe evidence (not mentioned in the editorial) that suggests that it is not the protein oligomers, per se, that damage neurons. Instead, neurons are damaged by an unseen sequence(s) of chemical reactions that generate reactive oxygen species (ROS), and it is the ROS that cause both protein aggregation and neurotoxicity. The latter “proteooxidot... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=4856373 Wed, 18 May 2011 21:23:50 +0100 4856373 http://www.medworm.com/index.php?rid=4833554&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Faj377v7612708535%2F Abstract  Activated microglial cells, which are the resident macrophages of the central nervous system, surround amyloid β-plaques in Alzheimer’s disease (AD) brains. Inflammation including microglial activation may contribute in AD pathogenesis, and biomarkers for this process may thus be of value to study AD pathogenesis and might facilitate development of therapies targeting these cells. We therefore examined cerebrospinal fluid (CSF) biomarkers in patients with AD, other dementias, mild cognitive impairment and in healthy controls. Samples were analyzed for markers with known association to macrophage activity, including chitotriosidase, YKL-40 (CHI3L1, HC gp-39) and chemokine CC motif ligand 2 (CCL2, MCP1). Patients with AD had higher chitotriosidase activity than c... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=4833554 Thu, 12 May 2011 16:40:48 +0100 4833554 http://www.medworm.com/index.php?rid=4823373&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe26j86482xj81181%2F Abstract  Aggregation of amyloid-beta is one of the major characteristics in brains of patients with Alzheimer’s disease (AD). Although several mechanisms behind the formation of such aggregates have been suggested the regulatory factors are still unknown. The present study aimed at investigating the association of lysyl oxidase-like 1 (LOXL1) polymorphisms with AD diagnosis and cerebrospinal fluid biomarkers (CSF) for the disease. Proteins of the lysyl oxidase (LOX) family are involved in cross-linking extracellular matrix proteins to insoluble fibers and have been associated with neurodegenerative diseases including AD. Genetic polymorphisms in LOXL1 (rs1048661, rs3825942, and rs2165241) have been linked to exfoliation syndrome and exfoliation glaucoma, conditions that ha... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=4823373 Wed, 11 May 2011 05:51:33 +0100 4823373 http://www.medworm.com/index.php?rid=4443158&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh6l527385102446t%2F Abstract  Multiple sclerosis frequently affects the optic apparatus, particularly optic chiasm and nerves. Here, we have reported the structural and molecular characteristics of remyelination in the adult rat optic chiasm and nerves. Moreover, considering the proximity of optic chiasm and 3rd ventricle, we have tried to determine if proliferating cells residing in 3rd ventricle region are able to migrate in response to experimental demyelination of the optic chiasm. Following local demyelination by lysolecithin, remyelination pattern in longitude of optic chiasm and proximal nerves was investigated using myelin staining and marker genes expression. Furthermore, cell tracing was carried out using BrdU labeling of proliferating cells prior to gliotoxin injection. Morphometric... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=4443158 Thu, 03 Feb 2011 21:11:07 +0100 4443158 http://www.medworm.com/index.php?rid=5164457&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy37214830651292h%2F Abstract  The peripheral nervous system (PNS), with all its branches and connections, is so complex that it is impossible to study all components at the light or electron microscopic level in any individual case; nevertheless, in certain diseases a simple nerve biopsy may suffice to arrive at a precise diagnosis. Structural changes of the PNS in neuropathies of the Charcot-Marie-Tooth (CMT) typ and related disorders comprise various components of the PNS. These include peripheral motor, sensory, and autonomous neurons with their axons, Schwann cells, and myelin sheaths in the radicular and peripheral nerves as well as satellite cells in spinal and autonomous ganglia. Astrocytes, oligodendroglial cells, and microglial cells around motor neurons in the anterior horn and aroun... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=5164457 Mon, 17 Jan 2011 20:07:40 +0100 5164457 http://www.medworm.com/index.php?rid=4328003&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb3773u42753gk130%2F Abstract  The clathrin assembly protein, CALM, promotes the assembly of clathrin-coated vesicles. In a previous study, we showed that CALM controls the level of the synaptic vesicle protein VAMP2 at the plasma membrane by regulating VAMP2 endocytosis. Here, we provide evidence that CALM also influences the cell surface level of the AMPA receptor subunit GluR2. Although mechanistic details as well as the physiological relevance of CALM and GluR2 in the neuron have yet to be established, CALM-mediated trafficking could function as a component of a dedicated system for controlling postsynaptic abundance of GluR2. Content Type Journal ArticlePages 1-3DOI 10.1007/s12017-010-8142-6Authors Asaff Harel, Laboratory of Neurosciences, National Institute on Aging Intramural Resear... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=4328003 Fri, 07 Jan 2011 14:51:41 +0100 4328003 http://www.medworm.com/index.php?rid=4273549&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw62342p23087n1u4%2F Abstract  The aim of this review is to evaluate the evidentiary base supporting the hypothesis that the increased hazard for obesity in mood disorder populations (and vice versa) is a consequence of shared pathophysiological pathways. We conducted a PubMed search of all English-language articles with the following search terms: obesity, inflammation, hypothalamic-pituitary-adrenal axis, insulin, cognition, CNS, and neurotransmitters, cross-referenced with major depressive disorder and bipolar disorder. The frequent co-occurrence of mood disorders and obesity may be characterized by interconnected pathophysiology. Both conditions are marked by structural and functional abnormalities in multiple cortical and subcortical brain regions that subserve cognitive and/or affective p... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=4273549 Thu, 16 Dec 2010 18:27:12 +0100 4273549 http://www.medworm.com/index.php?rid=4247181&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb5672t66721g88j0%2F Abstract  Alzheimer’s disease is the most widespread form of dementia. Its histopathological hallmarks include vascular and extracellular β-amyloid (Aβ) deposition and intraneuronal neurofibrillary tangles (NFTs). Gradual decline of cognitive functions linked to progressive synaptic loss makes patients unable to store new information in the earlier stages of the pathology, later becoming completely dependent because they are unable to do even elementary daily life actions. Although more than a hundred years have passed since Alois Alzheimer described the first case of AD, and despite many years of intense research, there are still many crucial points to be discovered in the neuropathological pathway. The development of transgenic mouse models engineered with overexpress... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=4247181 Wed, 08 Dec 2010 17:43:28 +0100 4247181 http://www.medworm.com/index.php?rid=4180586&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F54j359v0833r65q0%2F Abstract  The childhood disorder spinal muscular atrophy (SMA) is caused by reduced expression of the survival motor neuron (SMN) protein. SMN is a multifunctional protein that has been implicated in the production, processing and transport of RNA and ribonucleoproteins (RNPs). Within the nucleus, SMN is predominantly targeted to Cajal bodies (CB), which are involved in the maturation and processing of several subclasses of RNPs. Here, we show that the SMN exon 2b–encoded domain (SMN2b) is independently sufficient to mediate CB targeting, but that the resulting bodies are less dynamic than those containing full-length SMN protein. We also show that while two SMN proteins harbouring SMA-causing point mutations (A2G and S262I) are efficiently targeted to CBs, they also displ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=4180586 Tue, 16 Nov 2010 19:31:14 +0100 4180586 http://www.medworm.com/index.php?rid=4069774&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv122023086235706%2F Abstract  Spinocerebellar ataxia 3 (SCA3) is a genetic disorder resulting from the expansion of the CAG repeats in the ATXN3 gene. The pathogenesis of SCA3 is based on the toxic function of the mutant ataxin-3 protein, but the exact mechanism of the disease remains elusive. Various types of transgenic mouse models explore different aspects of SCA3 pathogenesis, but a knock-in humanized mouse has not yet been created. The initial aim of this study was to generate an ataxin-3 humanized mouse model using a knock-in strategy. The human cDNA for ataxin-3 containing 69 CAG repeats was cloned from SCA3 patient and introduced into the mouse ataxin-3 locus at exon 2, deleting it along with exon 3 and intron 2. Although the human transgene was inserted correctly, the resulting mice ac... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=4069774 Thu, 14 Oct 2010 06:16:03 +0100 4069774 http://www.medworm.com/index.php?rid=4069775&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F448rxw757184h0lm%2F This study suggests that the promoter polymorphism (rs6311) can affect both transcription factor binding and promoter methylation, and this along with an individual’s stress response can impact the rate of HTR2A transcription in a genotype and methylation-dependent manner. This study can serve as an example for deciphering the molecular determinants of transcriptional regulation of major genes of medical importance by integrating functional genomics and SEM approaches. Confirmation in an independent study population is required. Content Type Journal ArticleDOI 10.1007/s12017-010-8138-2Authors Virginia R. Falkenberg, Division of Viral and Rickettsial Diseases, Centers for Disease Control & Prevention, Atlanta, GA 30333, USABrian M. Gurbaxani, Division of Viral and Rickettsial Di... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=4069775 Tue, 12 Oct 2010 16:52:44 +0100 4069775 http://www.medworm.com/index.php?rid=3996095&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk600hmj654361611%2F In conclusion, widespread and significantly lowered α7 nAChR densities were demonstrated in both TBI models. Our results suggest that a nearly similar TBI-induced decrease in the α7 density in the brain of immature and adult animals is found, even with the differences in species, age and experimental procedures. The alterations make the α7 nAChR a suitable target for drug development and neuroimaging after TBI. Content Type Journal ArticleDOI 10.1007/s12017-010-8136-4Authors Peter-Georg Hoffmeister, Institute of Radiopharmacy, Research Site Leipzig, Research Center Dresden-Rossendorf, Permoserstraße 15, 04318 Leipzig, GermanyCornelius K. Donat, Institute of Radiopharmacy, Research Site Leipzig, Research Center Dresden-Rossendorf, Permoserstraße 15, 04318 Leipzig, GermanyMart... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3996095 Tue, 21 Sep 2010 04:10:47 +0100 3996095 http://www.medworm.com/index.php?rid=3931086&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F56v217x243168131%2F Abstract  In 1974, Markesbery et al. thoroughly characterized and reported a large kindred with distal muscle weakness of late adult-onset that was autosomal dominantly inherited. Clinical evidence supported myopathy rather than the usual neuropathy expected with distal weakness. Postmortem examination of two patients documented myopathy and excluded anterior horn cell disease or peripheral neuropathy as the cause. Distinctive morphologic changes were present in muscle. Widely accepted as a distinct disease entity, this disorder has recently been characterized as one of a group of myofibrillar myopathies resulting from mutations in several muscle proteins. Studies of members of the original family have now identified the molecular defect to be a mutation in ZASP, Z-band alt... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3931086 Thu, 02 Sep 2010 08:24:40 +0100 3931086 http://www.medworm.com/index.php?rid=3905478&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft15u327030501h15%2F Abstract  Although the brain contains a high content of sphingolipids, we know relatively little about the roles that sphingolipids play in regulating neural functions. Once regarded only for their structural roles in maintaining the integrity of cellular and sub-cellular compartments, it is now apparent that many sphingolipid species are biologically active and play important roles in regulating signaling events. Recent technological and scientific advances are rapidly increasing our knowledge of the roles that sphingolipids play in regulating normal neural activity. Likewise, we are beginning to understand how perturbations in sphingolipid metabolism contribute to the pathogenesis of a variety of neurodegenerative conditions. In this special issue of NeuroMolecular Medici... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3905478 Wed, 25 Aug 2010 06:14:18 +0100 3905478 http://www.medworm.com/index.php?rid=3897743&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1157l6l508071852%2F Abstract  Sphingolipidoses constitute a large subgroup of lysosomal storage disorders (LSDs). Many of them are associated with a progressive neurodegeneration. As is the case for LSDs in general, most sphingolipidoses are caused by deficiencies in lysosomal hydrolases. However, accumulation of sphingolipids can also result from deficiencies in proteins involved in the transport or posttranslational modification of lysosomal enzymes, transport of lipids, or lysosomal membrane proteins required for transport of lysosomal degradation end products. The accumulation of sphingolipids in the lysosome together with secondary changes in the concentration and localization of other lipids may cause trafficking defects of membrane lipids and proteins, affect calcium homeostasis, induce... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3897743 Sat, 21 Aug 2010 16:45:36 +0100 3897743 http://www.medworm.com/index.php?rid=3819058&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw637t04282440w84%2F Abstract  Sphingolipids (SP) are a complex class of molecules found in essentially all eukaryotes and some prokaryotes and viruses where they influence membrane structure, intracellular signaling, and interactions with the extracellular environment. Because of the combinatorial nature of their biosynthesis, there are thousands of SP subspecies varying in the lipid backbones and complex phospho- and glycoheadgroups. Therefore, comprehensive or “sphingolipidomic” analyses (structure-specific, quantitative analyses of all SP, or at least all members of a critical subset) are needed to know which and how much of these subspecies are present in a system as a step toward understanding their functions. Mass spectrometry and related novel techniques are able to quantify a small ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3819058 Tue, 03 Aug 2010 15:01:22 +0100 3819058 http://www.medworm.com/index.php?rid=3785404&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fnm6266u91v5123k8%2F Content Type Journal ArticleCategory Review PaperDOI 10.1007/s12017-010-8131-9Authors Deborah Danner, University of Kentucky Alzheimer’s Disease Center and Sanders-Brown Center on Aging Lexington KY USAPaula C. Thomason, University of Kentucky Alzheimer’s Disease Center and Sanders-Brown Center on Aging Lexington KY USA Journal NeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 (Source: NeuroMolecular Medicine) NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3785404 Fri, 23 Jul 2010 12:09:16 +0100 3785404 http://www.medworm.com/index.php?rid=3774402&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3p765l3777760457%2F Content Type Journal ArticleCategory Review PaperDOI 10.1007/s12017-010-8127-5Authors Annadora J. Bruce-Keller, Louisiana State University System Pennington Biomedical Research Center 6400 Perkins Road Baton Rouge LA 70808-4124 USAJeffrey N. Keller, Louisiana State University System Pennington Biomedical Research Center 6400 Perkins Road Baton Rouge LA 70808-4124 USA Journal NeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 (Source: NeuroMolecular Medicine) NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3774402 Fri, 16 Jul 2010 19:48:07 +0100 3774402 http://www.medworm.com/index.php?rid=3774403&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw6x0w1m6851p2103%2F Abstract  Alzheimer’s disease (AD) is a common age-related chronic illness with latent, prodrome, and fully symptomatic dementia stages. Increased free radical injury to regions of brain is one feature of prodrome and dementia stages of AD; however, it also is associated with advancing age. This raises the possibility that age-related free radical injury to brain might be caused in part or in full by latent AD. We quantified free radical injury in the central nervous system with cerebrospinal fluid (CSF) F2-isoprostanes (IsoPs) in 421 clinically normal individuals and observed a significant increase over the adult human lifespan (P < 0.001). Using CSF amyloid (A) β42 and tau, we defined normality using results from 28 clinically normal individuals <50... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3774403 Fri, 16 Jul 2010 17:02:52 +0100 3774403 http://www.medworm.com/index.php?rid=3756004&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F63t2q6ju61j8t362%2F Content Type Journal ArticleCategory Review PaperDOI 10.1007/s12017-010-8129-3Authors D. Allan Butterfield, University of Kentucky Department of Chemistry, Center of Membrane Science, Sanders-Brown Center on Aging Lexington KY 40506 USA Journal NeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 (Source: NeuroMolecular Medicine) NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3756004 Tue, 13 Jul 2010 15:29:08 +0100 3756004 http://www.medworm.com/index.php?rid=3756005&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw5q1422547770748%2F Abstract  Dimebon was originally introduced as an antihistamine and subsequently investigated as a possible therapeutic for a variety of disorders, including Alzheimer’s disease. One putative mechanism underlying the neuroprotective properties of Dimebon is inhibition of mitochondrial permeability transition, based on the observation that Dimebon inhibited the swelling of rat liver mitochondria induced by calcium and other agents that induce permeability transition. Because liver and brain mitochondria differ substantially in their properties and response to conditions associated with opening of the permeability transition pore, we sought to determine whether Dimebon inhibited permeability transition in brain mitochondria. Dimebon reduced calcium-induced mitochondrial swe... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3756005 Tue, 13 Jul 2010 15:28:54 +0100 3756005 http://www.medworm.com/index.php?rid=3735372&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc676j82rh550q2t1%2F Abstract  He spent tens of thousands of hours peering through the oculars of a microscope at stained brain tissue sections from thousands of patients who died with or without a neurodegenerative disorder; most of those patients he had himself cared for and had removed and processed their brain tissues upon their death. His discerning mind, humble demeanor, optimism and patience were fundamental features of his character. Through his research discoveries and advocacy, Dr. William R. Markesbery fought for those millions of elderly Americans with Alzheimer’s disease (AD) and their families and friends. For over a decade, my laboratory was located directly above Dr. Markesbery’s in the Sanders-Brown Research Center on Aging at the University of Kentucky in Lexington. In thi... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3735372 Wed, 07 Jul 2010 16:37:12 +0100 3735372 http://www.medworm.com/index.php?rid=3735373&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F50r3058613r76g45%2F Content Type Journal ArticleCategory Review PaperDOI 10.1007/s12017-010-8125-7Authors D. Stephen Snyder, National Institute on Aging, National Institute of Health Division of Neuroscience Gateway Building, Room 350, 7201 Wisconsin Avenue Bethesda MD 20892-9205 USA Journal NeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 (Source: NeuroMolecular Medicine) NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3735373 Tue, 06 Jul 2010 17:06:57 +0100 3735373 http://www.medworm.com/index.php?rid=3735374&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc318h106w8686542%2F Abstract  Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the CNS. Oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), are target cells in MS. Although the etiology of MS is poorly known, new insights suggest oligodendrocyte apoptosis as one of the critical events followed by glial activation and infiltration of lymphocytes and macrophages. A major breakthrough in delineation of the mechanism of cell death, perivascular cuffing, and glial activation came from elucidation of the sphingolipid signal transduction pathway. The sphingolipid signal transduction pathway induces apoptosis, differentiation, proliferation, and growth arrest depending upon cell and receptor types, and downstream targets. Sphingomyelin, a major compon... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3735374 Tue, 06 Jul 2010 17:06:56 +0100 3735374 http://www.medworm.com/index.php?rid=3728157&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2856752g20421768%2F Content Type Journal ArticleCategory Review PaperDOI 10.1007/s12017-010-8123-9Authors D. Allan Butterfield, University of Kentucky Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging Lexington KY 40506-0055 USA Journal NeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 (Source: NeuroMolecular Medicine) NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3728157 Fri, 02 Jul 2010 19:51:29 +0100 3728157 http://www.medworm.com/index.php?rid=3700568&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8k43l320x764937t%2F Content Type Journal ArticleCategory Review PaperDOI 10.1007/s12017-010-8119-5Authors Creighton H. Phelps, National Institute on Aging Alzheimer’s Disease Centers Program, Division of Neuroscience 7201 Wisconsin Ave., Suite 350 Bethesda MD 20892-9205 USA Journal NeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 (Source: NeuroMolecular Medicine) NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3700568 Wed, 23 Jun 2010 20:13:03 +0100 3700568 http://www.medworm.com/index.php?rid=3700569&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F00t5xv0324832lrm%2F Abstract  Photoparoxysmal response (PPR) is characterized by abnormal visual sensitivity of the brain to photic stimulation. Frequently associated with idiopathic generalized epilepsies (IGEs), it might be an endophenotype for cortical excitability. Transient receptor potential cation (TRPC) channels are involved in the generation of epileptiform discharges, and TRPC4 constitutes the main TRPC channel in the central nervous system. The present study investigated an association of PPR with sequence variations of the TRPC4 gene. Thirty-five single nucleotide polymorphisms (SNP) within TRPC4 were genotyped in 273 PPR probands and 599 population controls. Association analyses were performed for the broad PPR endophenotype (PPR types I–IV; n = 273), a narrow model of ... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3700569 Wed, 23 Jun 2010 20:13:01 +0100 3700569 http://www.medworm.com/index.php?rid=3693175&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv042281175104116%2F Abstract  The public health burden of Alzheimer disease (AD), the most common neurodegenerative disease, threatens to explode in the middle of this century. Current FDA-approved AD treatments (e.g. cholinesterase inhibitors, NMDA-receptor agonists) do not provide a “cure”, but rather a transient alleviation of symptoms for some individuals. Other available therapies are few and of limited effectiveness so additional avenues are needed. Sphingolipid metabolism is a dynamic process that modulates the formation of a number of bioactive metabolites, or second messengers critical in cellular signaling and apoptosis. In brain, the proper balance of sphingolipids is essential for normal neuronal function, as evidenced by a number of severe brain disorders that are the result o... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3693175 Tue, 22 Jun 2010 18:37:24 +0100 3693175 http://www.medworm.com/index.php?rid=3668818&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F01180g8ln23ng73x%2F Abstract  Ceramide, a bioactive lipid, has been extensively studied and identified as an essential bioactive molecule in mediating cellular signaling pathways. Sphingomyelinase (SMase), (EC 3.1.4.12) catalyzes the cleavage of the phosphodiester bond in sphingomyelin (SM) to form ceramide and phosphocholine. In mammals, three Mg2+-dependent neutral SMases termed nSMase1, nSMase2 and nSMase3 have been identified. Among the three enzymes, nSMase2 is the most studied and has been implicated in multiple physiological responses including cell growth arrest, apoptosis, development and inflammation. In this review, we summarize recent findings for the cloned nSMases and discuss the insights for their roles in regulation ceramide metabolism and cellular signaling pathway. Conten... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3668818 Wed, 16 Jun 2010 07:18:32 +0100 3668818 http://www.medworm.com/index.php?rid=3654261&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq0k47871125g1q72%2F Content Type Journal ArticleCategory Review PaperDOI 10.1007/s12017-010-8117-7Authors Mark A. Lovell, University of Kentucky Department of Chemistry and Sanders-Brown Center on Aging Lexington KY 40536 USA Journal NeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 (Source: NeuroMolecular Medicine) NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3654261 Thu, 10 Jun 2010 17:42:39 +0100 3654261 http://www.medworm.com/index.php?rid=3654262&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F08207028702x5756%2F Content Type Journal ArticleCategory Review PaperDOI 10.1007/s12017-010-8118-6Authors Stephen W. Scheff, University of Kentucky Center on Aging 101 Sanders-Brown Lexington KY 40536-0230 USA Journal NeuroMolecular MedicineOnline ISSN 1559-1174Print ISSN 1535-1084 (Source: NeuroMolecular Medicine) NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3654262 Thu, 10 Jun 2010 17:42:38 +0100 3654262 http://www.medworm.com/index.php?rid=3611290&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F66v082g745656603%2F Abstract  Ceramide forms the backbone of all complex sphingolipids and has been the focus of considerable attention in the past few years due to the discovery that ceramide plays vital roles as an intracellular messenger. Ceramide, which consists of a sphingoid long chain base to which a fatty acid is N-acylated, is synthesized in mammals by a family of ceramide synthases (CerS), each of which uses a restricted subset of fatty acyl CoAs for N-acylation. Sphingolipids are found at high levels in nervous tissue, where they perform a variety of important functions in both the adult and the maturing brain. We now review what is known about the role of the acyl chain composition of ceramides and sphingolipids in normal brain development and in neurological diseases. Specifically,... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3611290 Tue, 25 May 2010 16:52:03 +0100 3611290 http://www.medworm.com/index.php?rid=3611291&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm312750567240620%2F Abstract  Here, we present a male infant with clinical signs of typical Leigh syndrome. The first symptom, myoclonus was presented already on the 5th day of life; at 7 months of age limb convulsions and cerebral paresis with hypotonia were developed. At the age of 11 months, MRI verified increased signal intensity in the entire mesencephalon and medulla oblongata; while gray matter proton spectroscopy revealed presence of lactate increase in the brain. At age of 17 months, the child died in cardiorespiratory arrest. After autopsy, the diagnosis of Leigh syndrome was established; using DNA isolated from skeletal muscle and liver, heteroplasmic (>50%) mitochondrial 11777C>A was detected in the fourth subunit of NADH dehydrogenase enzyme (MTND4) encodi... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3611291 Tue, 25 May 2010 16:52:02 +0100 3611291 http://www.medworm.com/index.php?rid=3567563&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F25532671533k0515%2F Abstract  Several investigations have reported that abnormalities in circadian rhythms might be related with the pathophysiology of psychiatric disorders, since many psychiatric patients have insomnia and sleep-awake disturbance. A recent animal study reported that Magel2, which encodes a member of the MAGE/necdin family of proteins, might be associated in the pathophysiology of psychiatric disorders. Magel2 gene knockout mice showed altered concentrations of both dopamine and serotonin in several parts of the brain compared with controls. In addition, the authors of that study detected a bilateral reduction in cortical volume in distinct regions of the Magel2 gene knockout mice brain, including focused regions in the parieto-temporal lobe of the cerebral cortex, the amygda... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3567563 Fri, 14 May 2010 09:36:24 +0100 3567563 http://www.medworm.com/index.php?rid=3502298&cid=s_36003_25_f&fid=36003&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj4q8t2256h5423rk%2F Abstract  As the resident innate immune cells of the central nervous system (CNS), microglia fulfil a critical role in maintaining tissue homeostasis and in directing and eliciting molecular responses to CNS damage. The human disease Multiple Sclerosis and animal models of inflammatory demyelination are characterized by a complex interplay between degenerative and regenerative processes, many of which are regulated and mediated by microglia. Cellular communication between microglia and other neural and immune cells is controlled to a large extent by the activity of cytokines. Here we review the role of cytokines as mediators and regulators of microglial activity in inflammatory demyelination, highlighting their importance in potentiating cell damage, promoting neuroprotecti... NeuroMolecular Medicine journals http://www.medworm.com/rss/comments.php?id=3502298 Thu, 22 Apr 2010 09:28:39 +0100 3502298 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