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122 records returned

Kinesin Light Chain 1 Gene Haplotypes in Three Conformational DiseasesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 a...
Source: NeuroMolecular Medicine - November 12, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Manganese Flux Across the Blood–Brain BarrierEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 hydro...
Source: NeuroMolecular Medicine - November 9, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Alzheimer’s Disease and Neuronal Network ActivityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 alte...
Source: NeuroMolecular Medicine - November 3, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Manganese and its Role in Parkinson’s Disease: From Transport to NeuropathologyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 S...
Source: NeuroMolecular Medicine - October 28, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Modelling Parkinson’s Disease in DrosophilaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 geneti...
Source: NeuroMolecular Medicine - October 23, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Phospholipases A2 and Inflammatory Responses in the Central Nervous SystemEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 t...
Source: NeuroMolecular Medicine - October 23, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Involvement of Fc Receptors in Disorders of the Central Nervous SystemEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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. Ab...
Source: NeuroMolecular Medicine - October 21, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

No Association of VEGF Polymorphims with Alzheimer’s DiseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 re...
Source: NeuroMolecular Medicine - October 20, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Synaptic Depression and Aberrant Excitatory Network Activity in Alzheimer’s Disease: Two Faces of the Same Coin?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: NeuroMolecular Medicine - October 16, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

A Clear and Present Danger: Endogenous Ligands of Toll-like ReceptorsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, HMGB...
Source: NeuroMolecular Medicine - October 14, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Paraoxonase 1 Polymorphisms Are Not Related with the Risk for Multiple SclerosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 po...
Source: NeuroMolecular Medicine - October 13, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

The Role of the Complement System and the Activation Fragment C5a in the Central Nervous SystemEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 seco...
Source: NeuroMolecular Medicine - September 17, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

The Therapeutic Potential of microRNAs in Nervous System Damage, Degeneration, and RepairEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ad...
Source: NeuroMolecular Medicine - September 17, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Translin-Associated Factor X Gene (TSNAX) may be Associated with Female major Depressive Disorder in the Japanese PopulationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 sampl...
Source: NeuroMolecular Medicine - September 17, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

microRNAs in Gliomas: Small Regulators of a Big ProblemEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 apo...
Source: NeuroMolecular Medicine - September 17, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Dietary Supplementation with S-Adenosyl Methionine Delays the Onset of Motor Neuron Pathology in a Murine Model of Amyotrophic Lateral SclerosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 Jo...
Source: NeuroMolecular Medicine - September 16, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Alzheimer’s Disease Amyloid β-Protein and Synaptic FunctionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 synapti...
Source: NeuroMolecular Medicine - September 16, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Are There Common Biochemical and Molecular Mechanisms Controlling Manganism and ParkisonismEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: NeuroMolecular Medicine - September 16, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Macro Role(s) of MicroRNAs in Fragile X Syndrome?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 n...
Source: NeuroMolecular Medicine - August 11, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Variation in RTN3 and PPIL2 Genes Does not Influence Platelet Membrane β-Secretase Activity or Susceptibility to Alzheimer’s Disease in the Northern Irish PopulationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 North...
Source: NeuroMolecular Medicine - August 9, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Interaction Between α-Synuclein and Metal Ions, Still Looking for a Role in the Pathogenesis of Parkinson’s DiseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 mod...
Source: NeuroMolecular Medicine - August 9, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Manganese and its Role in Parkinson’s Disease: From Transport to NeuropathologyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 effect...
Source: NeuroMolecular Medicine - August 5, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Exercise and Bipolar Disorder: A Review of Neurobiological MediatorsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, neurob...
Source: NeuroMolecular Medicine - July 31, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Interleukin-1 Beta −511C/T Genetic Polymorphism is Associated with Age of Onset of Geriatric DepressionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 fu...
Source: NeuroMolecular Medicine - July 25, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

MicroRNAs in Adult and Embryonic NeurogenesisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: NeuroMolecular Medicine - July 14, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Leukocyte Recruitment and Ischemic Brain InjuryEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 leukoc...
Source: NeuroMolecular Medicine - July 6, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Neonatal Estrogenic Effects upon the Male Rat Pituitary: Early Gonadotrophin Attenuation Precedes Long-term RecoveryEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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) immunoreac...
Source: NeuroMolecular Medicine - June 30, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Amyloid-β Induces a Caspase-mediated Cleavage of P2X4 to Promote PurinotoxicityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 re...
Source: NeuroMolecular Medicine - June 29, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Epileptic Seizures in AD PatientsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, neurotr...
Source: NeuroMolecular Medicine - June 26, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

NAD+ Availability and ProteotoxicityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 prote...
Source: NeuroMolecular Medicine - June 25, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

MicroRNAs in Mental Health: From Biological Underpinnings to Potential TherapiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 therapie...
Source: NeuroMolecular Medicine - June 20, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Possible Association of Prokineticin 2 Receptor Gene (PROKR2) with Mood Disorders in the Japanese PopulationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 He...
Source: NeuroMolecular Medicine - June 20, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

microRNAs in CNS DisordersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 exp...
Source: NeuroMolecular Medicine - June 18, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

A Homozygous Genetic Variant of Mitochondrial Uncoupling Protein 4 Exerts Protection Against the Occurrence of Multiple SclerosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 esse...
Source: NeuroMolecular Medicine - June 18, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Matrix Metalloproteinase-9 Gene and Bipolar Mood DisorderEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 h...
Source: NeuroMolecular Medicine - June 18, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

No Association Between Polymorphisms of Neuronal Oxide Synthase 1 Gene (NOS1) and Schizophrenia in a Japanese PopulationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: NeuroMolecular Medicine - June 10, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Gene Dysregulation in Huntington’s Disease: REST, MicroRNAs and BeyondEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 a...
Source: NeuroMolecular Medicine - May 21, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

microRNA Regulation of Synaptic PlasticityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, activate...
Source: NeuroMolecular Medicine - May 21, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Decline in Daily Running Distance Presages Disease Onset in a Mouse Model of ALSEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 distanc...
Source: NeuroMolecular Medicine - May 6, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Novel GDAP1 Mutation in a Turkish Family with CMT2K (CMT2K with Novel GDAP1 Mutation)Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 (IVS...
Source: NeuroMolecular Medicine - April 21, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Induction of Early Growth Response-1 Mediates Microglia Activation In Vitro But is Dispensable In VivoEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 dete...
Source: NeuroMolecular Medicine - April 14, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

CLOCK may Predict the Response to Fluvoxamine Treatment in Japanese Major Depressive Disorder PatientsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 Hamil...
Source: NeuroMolecular Medicine - April 5, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

AAV-mediated Local Delivery of Interferon-β for the Treatment of Retinoblastoma in Preclinical ModelsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 pro...
Source: NeuroMolecular Medicine - March 22, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Nicotinamide Prevents NAD+ Depletion and Protects Neurons Against Excitotoxicity and Cerebral Ischemia: NAD+ Consumption by SIRT1 may Endanger Energetically Compromised NeuronsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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. De...
Source: NeuroMolecular Medicine - March 14, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Botanical Phenolics and Brain HealthEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: NeuroMolecular Medicine - February 4, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Voltammetric Bioassay of Caffeine using Sensor ImplantEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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&n...
Source: NeuroMolecular Medicine - January 1, 2009 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Common Variations in 4p Locus are Related to Male Completed SuicideEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 &l...
Source: NeuroMolecular Medicine - December 30, 2008 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Creatine and Its Potential Therapeutic Value for Targeting Cellular Energy Impairment in Neurodegenerative DiseasesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: NeuroMolecular Medicine - November 13, 2008 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals

Human BDNF Isoforms are Differentially Expressed in Cocaine Addicts and are Sorted to the Regulated Secretory Pathway Independent of the Met66 SubstitutionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 c...
Source: NeuroMolecular Medicine - October 23, 2008 Category: Neurology Tags: NeuroMolecular Medicine Source Type: journals