Botanical Polyphenols Mitigate Microglial Activation and Microglia-Induced Neurotoxicity: Role of Cytosolic Phospholipase A 2
In this study, we investigate the action of botanical compounds and assess whether suppression of cPLA2 in microglia is involved in the neurotoxic effects on neurons. Differentiated SH-SY5Y neuroblastoma cells were used to test the neurotoxicity of conditioned medium from stimulated microglial cells, and WST-1 assay was used to assess for the cell viability of SH-SY5Y cells. Botanicals such as quercetin and honokiol (but not cyanidin-3-O-glucoside, 3CG) were effective in inhibiting LPS-induced nitric oxide (NO) production and phosphorylation of cPLA2. Conditioned medium from BV-2 cells stimulated with LPS or IFNγ cau...
Source: NeuroMolecular Medicine - June 23, 2016 Category: Neurology Source Type: research

Clinacanthus nutans Extracts Modulate Epigenetic Link to Cytosolic Phospholipase A 2 Expression in SH-SY5Y Cells and Primary Cortical Neurons
In this study, we examined the effects of C. nutans ethanol leaf extracts on epigenetic regulation of cPLA2 mRNA expression in SH-SY5Y human neuroblastoma cells and mouse primary cortical neurons. C. nutans modulated induction of cPLA2 expression in SH-SY5Y cells by histone deacetylase (HDAC) inhibitors, MS-275, MC-1568, and TSA. C. nutans extracts also inhibited histone acetylase (HAT) activity. Levels of cPLA2 mRNA expression were increased in primary cortical neurons subjected to 0.5-h oxygen–glucose deprivation injury (OGD). This increase was significantly inhibited by C. nutans treatment. Treatment of primary ne...
Source: NeuroMolecular Medicine - June 18, 2016 Category: Neurology Source Type: research

GC and VDR SNPs and Vitamin D Levels in Parkinson ’s Disease: The Relevance to Clinical Features
Abstract Vitamin D deficiency is suggested to be associated with Parkinson ’s disease (PD). Our aim was to investigate the serum 25-hydroxyvitamin D 3 (25OHD) levels of PD patients in Turkish cohort, to investigate any association of vitamin D binding protein (GC) genotypes with PD due to the significant role of GC in vitamin D transport, to determine whether vitamin D receptor (VDR) haplotype that we previously demonstrated to be a risk haplotype for AD is also a common haplotype for PD and to investigate any relevant consequence of serum 25OHD levels, GC or VDR genotypes on clinical features of PD. Three hundred ...
Source: NeuroMolecular Medicine - June 9, 2016 Category: Neurology Source Type: research

GC and VDR SNPs and Vitamin D Levels in Parkinson’s Disease: The Relevance to Clinical Features
Abstract Vitamin D deficiency is suggested to be associated with Parkinson’s disease (PD). Our aim was to investigate the serum 25-hydroxyvitamin D3 (25OHD) levels of PD patients in Turkish cohort, to investigate any association of vitamin D binding protein (GC) genotypes with PD due to the significant role of GC in vitamin D transport, to determine whether vitamin D receptor (VDR) haplotype that we previously demonstrated to be a risk haplotype for AD is also a common haplotype for PD and to investigate any relevant consequence of serum 25OHD levels, GC or VDR genotypes on clinical features of PD. Three hun...
Source: NeuroMolecular Medicine - June 9, 2016 Category: Neurology Source Type: research

Potent Protection Against MPP + -Induced Neurotoxicity via Activating Transcription Factor MEF2D by a Novel Derivative of Naturally Occurring Danshensu/Tetramethylpyrazine
Abstract Danshensu (DSS) and tetramethylpyrazine (TMP) are active ingredients of Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort that are widely used in oriental medicine. Structural combination of compounds with known biological activity may lead to the formation of a molecule with multiple properties or new function profile. In the current study, the neuroprotective effects of DT-010, a novel analogue in which TMP was coupled to DSS through an ester bond and two allyl groups at the carboxyl group, were evaluated in a cellular model of Parkinson’s disease (PD). As evidenced by the increase in cell ...
Source: NeuroMolecular Medicine - June 8, 2016 Category: Neurology Source Type: research

mTOR Signaling in Parkinson ’s Disease
Abstract As a key regulator of cell metabolism and survival, mechanistic target of rapamycin (mTOR) emerges as a novel therapeutic target for Parkinson ’s disease (PD). A growing body of research indicates that restoring perturbed mTOR signaling in PD models can prevent neuronal cell death. Nevertheless, molecular mechanisms underlying mTOR-mediated effects in PD have not been fully understood yet. Here, we review recent progress in characterizin g the association of mTOR signaling with PD risk factors and further discuss the potential roles of mTOR in PD. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - June 4, 2016 Category: Neurology Source Type: research

mTOR Signaling in Parkinson’s Disease
Abstract As a key regulator of cell metabolism and survival, mechanistic target of rapamycin (mTOR) emerges as a novel therapeutic target for Parkinson’s disease (PD). A growing body of research indicates that restoring perturbed mTOR signaling in PD models can prevent neuronal cell death. Nevertheless, molecular mechanisms underlying mTOR-mediated effects in PD have not been fully understood yet. Here, we review recent progress in characterizing the association of mTOR signaling with PD risk factors and further discuss the potential roles of mTOR in PD. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - June 4, 2016 Category: Neurology Source Type: research

Protective Effects of AGE and Its Components on Neuroinflammation and Neurodegeneration
Abstract Garlic (Allium sativum) is used for culinary and medicinal purposes in diverse cultures worldwide. When fresh garlic is soaked in aqueous ethanol under ambient environment over 4 months or longer, the majority of irritating taste and odor is eliminated and the antioxidant profile in the resulting aged garlic extract (AGE) changes significantly. Recently, AGE and its components have been demonstrated to exert neuroprotective effects in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and cerebral ischemia. Because of its health sup...
Source: NeuroMolecular Medicine - June 4, 2016 Category: Neurology Source Type: research

Changes in Binding of [ 123 I]CLINDE, a High-Affinity Translocator Protein 18  kDa (TSPO) Selective Radioligand in a Rat Model of Traumatic Brain Injury
This study demonstrates the applicability of [ 123 I]CLINDE for detailed regional and quantitative assessment of glial activity in experimental models of TBI. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - June 1, 2016 Category: Neurology Source Type: research

Biomarkers of Resilience in Stress Reduction for Caregivers of Alzheimer ’s Patients
Abstract Caregiving for a dementia patient is associated with increased risk of psychological and physical health problems. We investigated whether a mindfulness-based stress reduction (MBSR) training course for caregivers that closely models the MBSR curriculum originally established by the Center of Mindfulness at the University of Massachusetts may improve the psychological resilience of non-professional caregivers of Alzheimer ’s disease patients. Twenty adult non-professional caregivers of dementia patients participated in an 8-week MBSR training course. Caregiver stress, depression, burden, grief, and gene exp...
Source: NeuroMolecular Medicine - June 1, 2016 Category: Neurology Source Type: research

Correlation with Platelet Parameters and Genetic Markers of Thrombophilia Panel (Factor II g.20210G & gt;A, Factor V Leiden, MTHFR (C677T, A1298C), PAI-1, β-Fibrinogen, Factor XIIIA (V34L), Glycoprotein IIIa (L33P)) in Ischemic Strokes
In this study, we analyzed mean platelet volume, platelet count values and genetic thrombophilia markers of patients who have ischemic stroke history and searched the relationship with genetic predisposition of ischemic strokes and platelet parameters. A retrospective, clinical trial was performed by reviewing the ischemic stroke history (except cryptogenic events) of 599 patients and 100 controls. The results of the genetic thrombophilia panel were used to classify the study group and control group into low and high risk for thrombophilia groups. The high-risk group included patients homozygous/heterozygous for Factor II ...
Source: NeuroMolecular Medicine - June 1, 2016 Category: Neurology Source Type: research

PICALM rs3851179 Variant and Alzheimer ’s Disease in Asian Population
(Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - June 1, 2016 Category: Neurology Source Type: research

Synaptogenesis: Modulation by Availability of Membrane Phospholipid Precursors
Abstract Phospholipids are the main constituents of brain membranes. Formation of new membranes requires that uridine, the omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA), and choline, the three circulating precursors of major phospholipids, interact via the Kennedy pathway. Supplementation of laboratory rodents with uridine, DHA and choline enhances the amount of brain membranes as well as synaptic proteins and increases the number of dendritic spines, the essential cytological precursor of new synapses. Hence, the newly formed membranes are utilized for synaptogenesis which underlies incre...
Source: NeuroMolecular Medicine - June 1, 2016 Category: Neurology Source Type: research

Promoter Variation and Expression Levels of Inflammatory Genes IL1A, IL1B , IL6 and TNF in Blood of Spinocerebellar Ataxia Type 3 (SCA3) Patients
Abstract Age at onset in spinocerebellar ataxia type 3 (SCA3/MJD) is incompletely explained by the size of the CAG tract at the ATXN3 gene, implying the existence of genetic modifiers. A role of inflammation in SCA3 has been postulated, involving altered cytokines levels; promoter variants leading to alterations in cytokines expression could influence onset. Using blood from 86 SCA3 patients and 106 controls, this work aimed to analyse promoter variation of four cytokines (IL1A, IL1B, IL6 and TNF) and to investigate the association between variants detected and their transcript levels, evaluated by quantitative PC...
Source: NeuroMolecular Medicine - May 31, 2016 Category: Neurology Source Type: research

Plasma Amyloid Beta 1-42 and DNA Methylation Pattern Predict Accelerated Aging in Young Subjects with Down Syndrome
Abstract Gene methylation is an age-related dynamic process that influences diseases. Premature aging and disturbed methylation are components of Down syndrome (DS). We studied blood biomarkers and DNA methylation (DNAm) of three CpG sites (ASPA, ITGA2B, and PDE4C) in 60 elderly subjects (mean age = 68 years), 31 subjects with DS (12.1 years) and 44 controls (12.8 years). Plasma concentrations of amyloid beta (Aβ) 1-42 and biomarkers of methylation were measured in the young groups. Subjects with DS had significantly higher concentrations of plasma S-adenosylhomocysteine (SAH) and A&b...
Source: NeuroMolecular Medicine - May 27, 2016 Category: Neurology Source Type: research

The Diversity of Spine Synapses in Animals
Abstract Here we examine the structure of the various types of spine synapses throughout the animal kingdom. Based on available evidence, we suggest that there are two major categories of spine synapses: invaginating and non-invaginating, with distributions that vary among different groups of animals. In the simplest living animals with definitive nerve cells and synapses, the cnidarians and ctenophores, most chemical synapses do not form spine synapses. But some cnidarians have invaginating spine synapses, especially in photoreceptor terminals of motile cnidarians with highly complex visual organs, and also in so...
Source: NeuroMolecular Medicine - May 26, 2016 Category: Neurology Source Type: research

Metformin Protects Cells from Mutant Huntingtin Toxicity Through Activation of AMPK and Modulation of Mitochondrial Dynamics
In this study, we showed that metformin rescued cells from mutant huntingtin (HTT)-induced toxicity, as indicated by reduced lactate dehydrogenase (LDH) release from cells and preserved ATP levels in cells expressing mutant HTT. Further mechanistic study indicated that metformin activated AMP-activated protein kinase (AMPK) and that inhibition of AMPK activation reduced its protective effects on mutant HTT toxicity, suggesting that AMPK mediates the protection of metformin in HD cells. Furthermore, metformin treatment prevented mitochondrial membrane depolarization and excess fission and modulated the disturbed mitochondri...
Source: NeuroMolecular Medicine - May 25, 2016 Category: Neurology Source Type: research

A Novel Association of the Suppressor of Cytokine Signaling 1 (SOCS1) Gene Polymorphisms in Ischemic Stroke Patients
We examined 475 patients with ischemic stroke and 486 normal controls. Three SNPs (rs243327, rs243330, and rs33932899) of SOCS1 gene were determined for TaqMan genotyping assays. We also classified these case samples in depth by complications with hypertension or diabetes and by ischemic stroke subtypes. When adjusting models by multiple factor analysis by logistic regression, then calculated 10,000 permutations were performed for each model to correct the multiple test. Under additive model, the rs243327 was associated with ischemic stroke with hypertension (p = 0.047). Under heterozygous model, the rs33932899 a...
Source: NeuroMolecular Medicine - May 23, 2016 Category: Neurology Source Type: research

Withania somnifera and Its Withanolides Attenuate Oxidative and Inflammatory Responses and Up-Regulate Antioxidant Responses in BV-2 Microglial Cells
This study is aimed to investigate anti-inflammatory and anti-oxidative properties of this botanical and its two withanolide constituents, namely, Withaferin A and Withanolide A, using the murine immortalized BV-2 microglial cells. Ashwagandha extracts not only effectively inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and reactive oxygen species (ROS) production in BV-2 cells, but also stimulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, leading to induction of heme oxygenase-1 (HO-1), both in the presence and absence of LPS. Although the withanolides were also capable of inhibiting LPS...
Source: NeuroMolecular Medicine - May 21, 2016 Category: Neurology Source Type: research

Targeting MicroRNAs Involved in the BDNF Signaling Impairment in Neurodegenerative Diseases
Abstract Neurodegenerative diseases are becoming an ever-increasing problem in aging populations. Low levels of brain-derived neurotrophic factor (BDNF) have previously been associated with the pathogenesis of numerous neurodegenerative diseases. Recently, microRNAs (miRNAs) have been proposed as potential novel therapeutic targets for treating various diseases of the central nervous system (CNS), and interestingly, few studies have reported several miRNAs that downregulate the expression levels of BDNF. However, substantial challenges exist when attempting to translate these findings into practical anti-miRNA the...
Source: NeuroMolecular Medicine - May 21, 2016 Category: Neurology Source Type: research

Phytochemicals in Ischemic Stroke
Abstract Stroke is the second foremost cause of mortality worldwide and a major cause of long-term disability. Due to changes in lifestyle and an aging population, the incidence of stroke continues to increase and stroke mortality predicted to exceed 12 % by the year 2030. However, the development of pharmacological treatments for stroke has failed to progress much in over 20 years since the introduction of the thrombolytic drug, recombinant tissue plasminogen activator. These alarming circumstances caused many research groups to search for alternative treatments in the form of neuroprotectants. Here, we...
Source: NeuroMolecular Medicine - May 18, 2016 Category: Neurology Source Type: research

Preserving Brain Function in Aging: The Anti-glycative Potential of Berry Fruit
Abstract Advanced glycation end products (AGEs) are naturally occurring macromolecules that are formed in vivo by the non-enzymatic modification of proteins, lipids, or nucleic acids by sugar, even in the absence of hyperglycemia. In the diet, AGEs are found in animal products, and additional AGEs are produced when those foods are cooked at high temperatures. Studies have linked AGEs to various age-related physiological changes, including wrinkles, diabetic complications, and neurodegenerative disease, including Alzheimer’s disease. Dietary berry fruits have been shown to reduce the severity or slow the prog...
Source: NeuroMolecular Medicine - May 11, 2016 Category: Neurology Source Type: research

Clinacanthus nutans Protects Cortical Neurons Against Hypoxia-Induced Toxicity by Downregulating HDAC1/6
This study further opens a new avenue for the use of herbal medicines to regulate epigenetic control of brain injury. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - May 10, 2016 Category: Neurology Source Type: research

Does Concurrent Use of Some Botanicals Interfere with Treatment of Tuberculosis?
Abstract Millions of individuals with active TB do not receive recommended treatments, and instead may use botanicals, or use botanicals concurrently with established treatments. Many botanicals protect against oxidative stress, but this can interfere with redox-dependent activation of isoniazid and other prodrugs used for prophylaxis and treatment of TB, as suggested by results of a recent clinical trial of the South African botanical Sutherlandia frutescens (L.) R. Br. (Sutherlandia). Here we provide a brief summary of Sutherlandia’s effects upon rodent microglia and neurons relevant to tuberculosis of the...
Source: NeuroMolecular Medicine - May 7, 2016 Category: Neurology Source Type: research

Nutraceuticals in Parkinson’s Disease
Abstract Current pharmacological strategies for Parkinson’s disease (PD), the most common neurological movement disorder worldwide, are predominantly symptom relieving and are often plagued with undesirable side effects after prolonged treatment. Despite this, they remain as the mainstay treatment for PD due to the lack of better alternatives. Nutraceuticals are compounds derived from natural food sources that have certain therapeutic value and the advent of which has opened doors to the use of alternative strategies to tackle neurodegenerative diseases such as PD. Notably, nutraceuticals are able to positio...
Source: NeuroMolecular Medicine - May 4, 2016 Category: Neurology Source Type: research

Identification of miRNAs as Potential Biomarkers in Cerebrospinal Fluid from Amyotrophic Lateral Sclerosis Patients
Abstract Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disorder. Since no diagnostic laboratory test exists, the identification of specific biomarkers could be fundamental in clinical practice. microRNAs (miRNAs) are considered promising biomarkers for neurodegenerative diseases. The aim of the study was to identify a CSF miRNA set that could differentiate ALS from non-ALS condition. miRNA profiling in CSF from ALS patients (n = 24; eight with C9orf72 expansion) and unaffected control subjects (n = 24) by quantitative reverse transcription PCR identified fourteen...
Source: NeuroMolecular Medicine - April 27, 2016 Category: Neurology Source Type: research

Association Between Osteopontin Gene Polymorphisms and Cerebral Palsy in a Chinese Population
Abstract Cerebral palsy (CP) is a neurological disorder affecting movement and posture that develops as a complication of prenatal, perinatal, and postnatal brain injury. Such non-progressive brain injury is often accompanied by neonatal encephalopathy and inflammation. The widely expressed soluble cytokine osteopontin (OPN) plays an important role in inflammation and neurological protection. Therefore, it is of great interest to study the relationship between CP and genetic variants of OPN. To explore the genetic association between OPN gene single nucleotide polymorphisms (SNPs) and CP in the Chinese Han populat...
Source: NeuroMolecular Medicine - April 25, 2016 Category: Neurology Source Type: research

Scutellarin as a Potential Therapeutic Agent for Microglia-Mediated Neuroinflammation in Cerebral Ischemia
Abstract The cerebral ischemia is one of the most common diseases in the central nervous system that causes progressive disability or even death. In this connection, the inflammatory response mediated by the activated microglia is believed to play a central role in this pathogenesis. In the event of brain injury, activated microglia can clear the cellular debris and invading pathogens, release neurotrophic factors, etc., but in chronic activation microglia may cause neuronal death through the release of excessive inflammatory mediators. Therefore, suppression of microglial over-reaction and microglia-mediated neur...
Source: NeuroMolecular Medicine - April 21, 2016 Category: Neurology Source Type: research

Trans-Cinnamaldehyde, An Essential Oil in Cinnamon Powder, Ameliorates Cerebral Ischemia-Induced Brain Injury via Inhibition of Neuroinflammation Through Attenuation of iNOS, COX-2 Expression and NFκ-B Signaling Pathway
Abstract Trans-cinnamaldehyde (TCA), an essential oil in cinnamon powder, may have beneficial effects as a treatment for stroke which is the second leading cause of death worldwide. Post-ischemic inflammation induces neuronal cell damage after stroke, and activation of microglia, in particular, has been thought as the main contributor of proinflammatory and neurotoxic factors. The purpose of this study was to investigate the neuroprotective effects of TCA in an animal model of ischemia/reperfusion (I/R)-induced brain injury and the neuroprotective mechanism was verified in LPS-induced inflammation of BV-2 microgli...
Source: NeuroMolecular Medicine - April 18, 2016 Category: Neurology Source Type: research

Neuro-protective Mechanisms of Lycium barbarum
Abstract Neuronal diseases, including retinal disorders, stroke, Alzheimer’s disease, Parkinson’s disease and spinal cord injury, affect a large number of people worldwide and cause heavy social and economic burdens. Although many efforts have been made by scientists and clinicians to develop novel drug and healthcare strategies, few of them received satisfactory outcomes to date. Lycium barbarum is a traditional homology of medicine and food in Chinese medicine, with the capability to nourish the eyes, liver and kidneys. Recent studies have also explored its powerful neuro-protective effects on a numb...
Source: NeuroMolecular Medicine - March 31, 2016 Category: Neurology Source Type: research

Effects of Anti-NMDA Antibodies on Functional Recovery and Synaptic Rearrangement Following Hemicerebellectomy
Abstract The compensation that follows cerebellar lesions is based on synaptic modifications in many cortical and subcortical regions, although its cellular mechanisms are still unclear. Changes in glutamatergic receptor expression may represent the synaptic basis of the compensated state. We analyzed in rats the involvement of glutamatergic system of the cerebello-frontal network in the compensation following a right hemicerebellectomy. We evaluated motor performances, spatial competencies and molecular correlates in compensated hemicerebellectomized rats which in the frontal cortex contralateral to the hemicereb...
Source: NeuroMolecular Medicine - March 30, 2016 Category: Neurology Source Type: research

The Role of a Catechol- O -Methyltransferase (COMT) Val158Met Genetic Polymorphism in Schizophrenia: A Systematic Review and Updated Meta-analysis on 32,816 Subjects
Abstract An association between a catechol-O-methyltransferase (COMT) Val156Met (rs4680) polymorphism and schizophrenia has been reported in the literature, although no conclusive outcomes have been attained. The aim of this study was to evaluate the association of the COMT Val108/158Met polymorphism with schizophrenia in a systematic review and meta-analysis. We performed a keyword search on PubMed and EBSCO databases. All English language case–control studies published up to April 2015 were selected. A total of 67 studies were selected for inclusion. The genotype distribution of subjects with schizophrenia...
Source: NeuroMolecular Medicine - March 28, 2016 Category: Neurology Source Type: research

Effects of Maternal Marginal Iodine Deficiency on Dendritic Morphology in the Hippocampal CA1 Pyramidal Neurons in Rat Offspring
Abstract Although the salt iodization programmes are taken to control iodine deficiency (ID), some regions are still suffering from marginal ID. During pregnancy, marginal ID frequently leads to subtle insufficiency of thyroid hormones, characterized as low serum T4 levels. Therefore, the present research was to explore the effects of maternal marginal ID exposure on dendritic arbor growth in the hippocampal CA1 region and the underlying mechanisms. We established Wistar rat models with ID diet during pregnancy and lactation. The overall daily iodine intakes of the rats were estimated as 7.0, 5.0 and 1.5 μ...
Source: NeuroMolecular Medicine - March 26, 2016 Category: Neurology Source Type: research

Biomarkers of Resilience in Stress Reduction for Caregivers of Alzheimer’s Patients
Abstract Caregiving for a dementia patient is associated with increased risk of psychological and physical health problems. We investigated whether a mindfulness-based stress reduction (MBSR) training course for caregivers that closely models the MBSR curriculum originally established by the Center of Mindfulness at the University of Massachusetts may improve the psychological resilience of non-professional caregivers of Alzheimer’s disease patients. Twenty adult non-professional caregivers of dementia patients participated in an 8-week MBSR training course. Caregiver stress, depression, burden, grief, and g...
Source: NeuroMolecular Medicine - March 17, 2016 Category: Neurology Source Type: research

PICALM rs3851179 Variant and Alzheimer’s Disease in Asian Population
(Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - March 17, 2016 Category: Neurology Source Type: research

Re: “PICALM Gene rs3851179 Polymorphism Contributes to Alzheimer’s Disease in an Asian Population”
Abstract Liu et al. have carried out a meta-analysis of case–control studies to investigate the association between PICALM gene rs3851179 polymorphism and Alzheimer’s disease in an Asian population. However, several important issues should be noted. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - March 14, 2016 Category: Neurology Source Type: research

Changes in Binding of [ 123 I]CLINDE, a High-Affinity Translocator Protein 18 kDa (TSPO) Selective Radioligand in a Rat Model of Traumatic Brain Injury
This study demonstrates the applicability of [123I]CLINDE for detailed regional and quantitative assessment of glial activity in experimental models of TBI. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - March 11, 2016 Category: Neurology Source Type: research

Correlation with Platelet Parameters and Genetic Markers of Thrombophilia Panel (Factor II g.20210G>A, Factor V Leiden, MTHFR (C677T, A1298C), PAI-1, β-Fibrinogen, Factor XIIIA (V34L), Glycoprotein IIIa (L33P)) in Ischemic Strokes
In this study, we analyzed mean platelet volume, platelet count values and genetic thrombophilia markers of patients who have ischemic stroke history and searched the relationship with genetic predisposition of ischemic strokes and platelet parameters. A retrospective, clinical trial was performed by reviewing the ischemic stroke history (except cryptogenic events) of 599 patients and 100 controls. The results of the genetic thrombophilia panel were used to classify the study group and control group into low and high risk for thrombophilia groups. The high-risk group included patients homozygous/heterozygous for Factor II ...
Source: NeuroMolecular Medicine - March 7, 2016 Category: Neurology Source Type: research

Vorinostat Modulates the Imbalance of T Cell Subsets, Suppresses Macrophage Activity, and Ameliorates Experimental Autoimmune Uveoretinitis
Abstract The purpose of the study was to investigate the anti-inflammatory efficiency of vorinostat, a histone deacetylase inhibitor, in experimental autoimmune uveitis (EAU). EAU was induced in female C57BL/6J mice immunized with interphotoreceptor retinoid-binding protein peptide. Vorinostat or the control treatment, phosphate-buffered saline, was administrated orally from 3 days before immunization until euthanasia at day 21 after immunization. The clinical and histopathological scores of mice were graded, and the integrity of the blood–retinal barrier was examined by Evans blue staining. T helper ce...
Source: NeuroMolecular Medicine - January 21, 2016 Category: Neurology Source Type: research

Changes in Dopamine Signalling Do Not Underlie Aberrant Hippocampal Plasticity in a Mouse Model of Huntington’s Disease
Abstract Altered dopamine receptor labelling has been demonstrated in presymptomatic and symptomatic Huntington’s disease (HD) gene carriers, indicating that alterations in dopaminergic signalling are an early event in HD. We have previously described early alterations in synaptic transmission and plasticity in both the cortex and hippocampus of the R6/1 mouse model of Huntington’s disease. Deficits in cortical synaptic plasticity were associated with altered dopaminergic signalling and could be reversed by D1- or D2-like dopamine receptor activation. In light of these findings we here investigated whe...
Source: NeuroMolecular Medicine - January 18, 2016 Category: Neurology Source Type: research

Proteomic Profiling in the Brain of CLN1 Disease Model Reveals Affected Functional Modules
Abstract Neuronal ceroid lipofuscinoses (NCL) are the most commonly inherited progressive encephalopathies of childhood. Pathologically, they are characterized by endolysosomal storage with different ultrastructural features and biochemical compositions. The molecular mechanisms causing progressive neurodegeneration and common molecular pathways linking expression of different NCL genes are largely unknown. We analyzed proteome alterations in the brains of a mouse model of human infantile CLN1 disease—palmitoyl-protein thioesterase 1 (Ppt1) gene knockout and its wild-type age-matched counterpart at different...
Source: NeuroMolecular Medicine - December 26, 2015 Category: Neurology Source Type: research

ApoA1, ApoJ and ApoE Plasma Levels and Genotype Frequencies in Cerebral Amyloid Angiopathy
Abstract The involvement of apolipoproteins, such as the ApoE4 isoform, in Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA) highlights the fact that certain lipid carriers may participate in soluble β-amyloid (Aβ) transport. Our general aim was to characterize the soluble levels of the apolipoproteins apoE, apoA1 and apoJ/clusterin and their genotype status in patients with CAA. We analyzed the genotypes frequency of APOA1 (rs5069, rs670), CLU (rs11136000, rs1532278, rs7012010, rs9331888) and APOE (rs429358, rs7412) in a cohort of patients with CAA-associated intracerebral hemorrhage ...
Source: NeuroMolecular Medicine - December 14, 2015 Category: Neurology Source Type: research

Does PGC1α/FNDC5/BDNF Elicit the Beneficial Effects of Exercise on Neurodegenerative Disorders?
Abstract Neurodegenerative disorders such as Alzheimer’s, Parkinson’s and Huntington’s diseases have high prevalence among the elderly. Many strategies have been established to alleviate the symptoms experienced by affected individuals. Recent studies have shown that exercise helps patients with neurological disorders to regain lost physical abilities. PGC1α/FNDC5/BDNF has emerged recently as a critical pathway for neuroprotection. PGC1α is a highly conserved co-activator of transcription factors that preserves and protects neurons against destruction. PGC1α regulates FNDC5 ...
Source: NeuroMolecular Medicine - November 26, 2015 Category: Neurology Source Type: research

The RS685012 Polymorphism of ACCN2, the Human Ortholog of Murine Acid-Sensing Ion Channel (ASIC1) Gene, is Highly Represented in Patients with Panic Disorder
Abstract Panic disorder (PD) is a disabling anxiety disorder that is characterized by unexpected, recurrent panic attacks, associated with fear of dying and worrying about possible future attacks or other behavioral changes as a consequence of the attacks. The acid-sensing ion channels (ASICs) are a family of proton-sensing channels expressed throughout the nervous system. Their activity is linked to a variety of behaviors including fear, anxiety, pain, depression, learning, and memory. The human analog of ASIC1a is the amiloride-sensitive cation channel 2 (ACCN2). Adenosine A2A receptors are suggested to play an ...
Source: NeuroMolecular Medicine - November 20, 2015 Category: Neurology Source Type: research

The Variant p.(Arg183Trp) in SPTLC2 Causes Late-Onset Hereditary Sensory Neuropathy
We describe two families with autosomal dominant HSAN1C caused by a new variant in SPTLC2, c.547C>T, p.(Arg183Trp). The variant changed a conserved amino acid and was not found in public variant databases. All patients had a relatively mild progressive distal sensory impairment, with onset after age 50. Small fibers were affected early, leading to abnormalities on quantitative sensory testing. Sural biopsy revealed a severe chronic axonal neuropathy with subtotal loss of myelinated axons, relatively preserved number of non-myelinated fibers and no signs for regeneration. Skin biopsy with PGP9.5 labeling showed lack of i...
Source: NeuroMolecular Medicine - November 16, 2015 Category: Neurology Source Type: research

Genetic Factors Affecting Late-Onset Alzheimer’s Disease Susceptibility
Abstract Alzheimer’s disease is considered a progressive brain disease in the older population. Late-onset Alzheimer’s disease (LOAD) as a multifactorial dementia has a polygenic inheritance. Age, environment, and lifestyle along with a growing number of genetic factors have been reported as risk factors for LOAD. Our aim was to present results of LOAD association studies that have been done in northwestern Iran, and we also explored possible interactions with apolipoprotein E (APOE) status. We re-evaluated the association of these markers in dominant, recessive, and additive models. In all, 160 LOAD a...
Source: NeuroMolecular Medicine - November 9, 2015 Category: Neurology Source Type: research

Targeted Gene Resequencing (Astrochip) to Explore the Tripartite Synapse in Autism–Epilepsy Phenotype with Macrocephaly
Abstract The frequent co-occurrence of autism spectrum disorders (ASD) and epilepsy, or paroxysmal EEG abnormalities, defines a condition termed autism–epilepsy phenotype (AEP). This condition results, in some cases , from dysfunctions of glial inwardly rectifying potassium channels (Kir), which are mainly expressed in astrocytes where they mediate neuron–glia communication. Macrocephaly is also often comorbid with autism–epilepsy (autism–epilepsy phenotype with macrocephaly, MAEP), and it is tempting to hypothesize that shared pathogenic mechanisms might explain concurrence of these con...
Source: NeuroMolecular Medicine - November 4, 2015 Category: Neurology Source Type: research

Astrocyte-Dependent Vulnerability to Excitotoxicity in Spermine Oxidase-Overexpressing Mouse
Abstract Transgenic mice overexpressing spermine oxidase (SMO) in the cerebral cortex (Dach-SMO mice) showed increased vulnerability to excitotoxic brain injury and kainate-induced epileptic seizures. To investigate the mechanisms by which SMO overexpression leads to increased susceptibility to kainate excitotoxicity and seizure, in the cerebral cortex of Dach-SMO and control mice we assessed markers for astrocyte proliferation and neuron loss, and the ability of kainate to evoke glutamate release from nerve terminals and astrocyte processes. Moreover, we assessed a possible role of astrocytes in an in vitro model...
Source: NeuroMolecular Medicine - November 3, 2015 Category: Neurology Source Type: research

Genetic, Epigenetic, and Environmental Factors Influencing Neurovisceral Integration of Cardiovascular Modulation: Focus on Multiple Sclerosis
Abstract Thought to be an autoimmune inflammatory CNS disease, multiple sclerosis (MS) involves multiple pathologies with heterogeneous clinical presentations. An impaired neurovisceral integration of cardiovascular modulation, indicated by sympathetic and parasympathetic autonomic nervous system (ANS) dysfunction, is among common MS clinical presentations. ANS dysfunction could not only enhance MS inflammatory and neurodegenerative processes, but can also lead to clinical symptoms such as depression, fatigue, sleep disorder, migraine, osteoporosis, and cerebral hemodynamic impairments. Therefore, factor...
Source: NeuroMolecular Medicine - October 26, 2015 Category: Neurology Source Type: research

Role of Rho Kinase and Fasudil on Synaptic Plasticity in Multiple Sclerosis
Abstract In addition to myelin loss and oligodendrocyte injury, axonal damage is a major cause of irreversible neurological disability in multiple sclerosis (MS). A series of studies have demonstrated that Rho kinase (ROCK) is involved in synaptic plasticity of neurons. Here, we found that ROCK activity in MS serum was elevated compared with serum from healthy controls. In experimental autoimmune encephalomyelitis (EAE), ROCK activity was also increased in serum, spleen, brain and spinal cord. Neuron injury with scratch and TNF-α stimulation induced the up-regulation of ROCK activity. When serum of MS pa...
Source: NeuroMolecular Medicine - October 19, 2015 Category: Neurology Source Type: research