Involvement of IL-17 in Secondary Brain Injury After a Traumatic Brain Injury in Rats
This study suggests that IL-17 is involved in secondary brain injury after TBI. Administering an IL-2 3 inhibitor and thereby blocking the IL-23/IL-17 axis may be beneficial in the treatment of TBI. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - September 15, 2017 Category: Neurology Source Type: research

Haplotype Study in SCA10 Families Provides Further Evidence for a Common Ancestral Origin of the Mutation
AbstractSpinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia and epilepsy. The disease is caused by a pentanucleotide ATTCT expansion in intron 9 of theATXN10 gene on chromosome 22q13.3. SCA10 has shown a geographical distribution throughout America with a likely degree of Amerindian ancestry from different countries so far. Currently available data suggest that SCA10 mutation might have spread out early during the peopling of the Americas. However, the ancestral origin of SCA10 mutation remains under speculation. Samples of SCA10 patients...
Source: NeuroMolecular Medicine - September 13, 2017 Category: Neurology Source Type: research

Mutation in GNE Downregulates Peroxiredoxin IV Altering ER Redox Homeostasis
AbstractGNE myopathy is a rare neuromuscular genetic disorder characterized by early adult onset and muscle weakness due to mutation in sialic acid biosynthetic enzyme, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). More than 180 different GNE mutations are known all over the world with unclear pathomechanism. Although hyposialylation of glycoproteins is speculated to be the major cause, but cellular mechanism leading to loss of muscle mass has not yet been deciphered. Besides sialic acid biosynthesis, GNE affects other cellular functions such as cell adhesion and apoptosis. In order to understand th...
Source: NeuroMolecular Medicine - September 11, 2017 Category: Neurology Source Type: research

Purine Biosynthesis Enzymes in Hippocampal Neurons
AbstractDespite reports implicating disrupted purine metabolism in causing a wide spectrum of neurological defects, the mechanistic details of purine biosynthesis in neurons are largely unknown. As an initial step in filling that gap, we examined the expression and subcellular distribution of three purine biosynthesis enzymes (PFAS, PAICS and ATIC) in rat hippocampal neurons. Using immunoblotting and high-resolution light and electron microscopic analysis, we find that all three enzymes are broadly distributed in hippocampal neurons with pools of these enzymes associated with mitochondria. These findings suggest a potentia...
Source: NeuroMolecular Medicine - September 2, 2017 Category: Neurology Source Type: research

Scavenger Receptor A Mediates the Clearance and Immunological Screening of MDA-Modified Antigen by M2-Type Macrophages
In this study, we investigated the uptake of malondialdehyde (MDA)-modified myelin oligodendrocyte glycoprotein (MOG) in the context of lipid peroxidation and its implications in CNS autoimmunity. The use of custom-produced fluorescently labeled versions of MOG or MDA-modified MOG enabled us to study and quantify the uptake by different macrophage populations and to identify the responsible receptor, namely SRA. The SRA-mediated uptake of MDA-modified MOG is roughly tenfold more efficient compared to that of the native form. Notably, this uptake is most strongly associated with anti-inflammatory M2-type macrophages. MDA-mo...
Source: NeuroMolecular Medicine - August 21, 2017 Category: Neurology Source Type: research

Isorhynchophylline Attenuates MPP + -Induced Apoptosis Through Endoplasmic Reticulum Stress- and Mitochondria-Dependent Pathways in PC12 Cells: Involvement of Antioxidant Activity
In this study, we found that isorhynchophylline (IRN) significantly attenuated 1-methyl-4-phenylpyridinium (MPP+)-induced apoptotic cell death and oxidative stress in PC12 cells. IRN markedly reduced MPP+-induced-ERS responses, indicative of inositol-requiring enzyme 1 (IRE1) phosphorylation and caspase-12 activation. Furthermore, IRN inhibits MPP+-triggered apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal Kinase (JNK) signaling-mediated mitochondria-dependent apoptosis pathway. IRN-mediated attenuation of endoplasmic reticulum modulator caspase-12 activation was abolished by diphenyleneiodonium (DPI) or IRE-1 ...
Source: NeuroMolecular Medicine - August 18, 2017 Category: Neurology Source Type: research

Association Between NOS1 Gene Polymorphisms and Schizophrenia in Asian and Caucasian Populations: A Meta-Analysis
AbstractSchizophrenia is a complex psychiatric disorder characterized by memory impairments with delusions and hallucinations. Several investigations have focused on determining the association between NOS1 (nitric oxide synthase-1) polymorphisms and risk of schizophrenia (SZ). However, the association of rs2682826, rs3782206, rs499776, rs3782219, rs41279104, rs3782221, rs1879417, rs4767540, rs561712, and rs6490121 polymorphisms with schizophrenia remains inconclusive. We performed a systematic meta-analysis for each polymorphism to determine its association with SZ by calculating their pooled odds ratio and 95% confidence...
Source: NeuroMolecular Medicine - August 9, 2017 Category: Neurology Source Type: research

Combination of EPA with Carotenoids and Polyphenol Synergistically Attenuated the Transformation of Microglia to M1 Phenotype Via Inhibition of NF- κB
AbstractMicroglia activation toward the M1 phenotype has been reported to contribute to the neurodegenerative processes and cognition alterations due to the release of pro-inflammatory mediators and cytokines. The aim of the present research was to assess the effectiveness of free fatty acids omega-3 preparations: eicosapentaenoic acid (EPA) or/and docosahexaenoic acid (DHA), carotenoids and phenolics combinations, in inhibiting the release of inflammatory mediators from activated microglia. Preincubation of BV-2 microglia cells with each of the FFAs omega-3 preparations in a range of 0.03 –2 μM together with...
Source: NeuroMolecular Medicine - August 4, 2017 Category: Neurology Source Type: research

VEGF-Mediated Cognitive and Synaptic Improvement in Chronic Cerebral Hypoperfusion Rats Involves Autophagy Process
AbstractChronic cerebral hypoperfusion (CCH) is associated with various neurodegenerative diseases characterized by cognitive impairment. Dozens of studies including ours have indicated that exogenous administration of vascular endothelial growth factor (VEGF) could exert effective cognitive protection during ischemia. Nevertheless, the underlying mechanism has not been well clarified. To address this issue, we explored the synaptic mechanisms in vivo since hippocampal synaptic function is essential to the learning and memory process. Besides, the role of autophagy in cognitive dysfunction under conditions of CCH is still ...
Source: NeuroMolecular Medicine - August 1, 2017 Category: Neurology Source Type: research

Novel CD137 Gene Polymorphisms and Susceptibility to Ischemic Stroke in the Northern Chinese Han Population
AbstractIschemic stroke is a leading cause of mortality and morbidity worldwide, and atherosclerosis is one of the major risk factors for this neurologic deficit. Recent studies have revealed the important role of CD137 in human atherosclerosis. Here, we analyzed the association of CD137 single nucleotide polymorphisms (SNPs) with ischemic stroke. We assessed three SNPs (rs161827, rs161818, and rs161810) of the CD137 gene and their association with ischemic stroke in a northern Chinese Han population. A total of 496 ischemic stroke patients and 486 gender-matched control subjects were genotyped. We classified these patient...
Source: NeuroMolecular Medicine - July 28, 2017 Category: Neurology Source Type: research

Experimental Autoimmune Encephalomyelitis Ameliorated by Passive Transfer of Polymerase 1-Silenced MOG35-55 Lymphatic Node Cells: Verification of a Novel Therapeutic Approach in Multiple Sclerosis
AbstractIn the current study, we present an innovative concept based on the knowledge that enhancing naturally occurring biological mechanisms is effective in preventing neuronal damage and maintaining low disease activity in about 15% of multiple sclerosis (MS) patients presenting the benign type of MS. Recently, we have demonstrated that low disease activity in benign MS is associated with suppression of RNA polymerase 1 (POL1) pathway; therefore, targeting POL1 transcription machinery as a strategy for suppressing active forms of MS is suggested. To further establish our approach, we aimed to suppress POL1 pathway by si...
Source: NeuroMolecular Medicine - July 28, 2017 Category: Neurology Source Type: research

Molecular Basis of Pediatric Brain Tumors
AbstractBrain tumors emerge as the second commonest type of pediatric solid tumors following hematologic malignancies. Genomic profiling of low- and high-grade gliomas, ependymomas and medulloblastomas has revealed chromosomal abnormalities and specific gene mutations which have been associated with aberrant activation of crucial signal transduction pathways, including mitogen-activated protein kinase, mammalian target of rapamycin and retinoblastoma tumor suppressor signaling. Furthermore, pediatric high-grade gliomas are associated with chromatin remodeling defects and somatic histone gene mutations that affect prognosis...
Source: NeuroMolecular Medicine - July 26, 2017 Category: Neurology Source Type: research

Mimicking Parkinson ’s Disease in a Dish: Merits and Pitfalls of the Most Commonly used Dopaminergic In Vitro Models
AbstractParkinson ’s disease (PD) is the second most common neurodegenerative disorder and has both unknown etiology and non-curative therapeutic options. Patients begin to present the classic motor symptoms of PD—tremor at rest, bradykinesia and rigidity—once 50–70% of the dopaminergic neurons of the nigrost riatal pathway have degenerated. As a consequence of this, it is difficult to investigate the early-stage events of disease pathogenesis. In vitro experimental models are used extensively in PD research because they present a controlled environment that enables the direct investigation of the e...
Source: NeuroMolecular Medicine - July 18, 2017 Category: Neurology Source Type: research

Joint Effects of GWAS SNPs in Coagulation System Confer Risk to Hypertensive Intracerebral Hemorrhage
AbstractRecent genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with coagulation system, including hemostatic factors and hematological phenotypes. However, few articles described the relationships between these SNPs and the risk of hemorrhagic stroke. The aim of our study was to evaluate the roles of these SNPs as risk factors and survival predictors for hemorrhagic stroke. Thirteen SNPs from GWAS in coagulation system were genotyped in a Chinese Han population including 1000 patients with hemorrhagic stroke (intracerebral hemorrhage, ICH  = 743; s...
Source: NeuroMolecular Medicine - July 17, 2017 Category: Neurology Source Type: research

An Inframe Trinucleotide Deletion in MTRR Exon 1 is Associated with the Risk of Spina Bifida
AbstractMaternal genetic variants of enzymes in folate –homocysteine metabolic network are significantly correlative with the risk of spina bifida. To survey the genetic causality, the genotypes of three women having spina bifida fetuses from two unrelated Chinese families were screened in candidate alleles. Polymerase chain reaction, capillary electr ophoresis and Sanger sequencing were employed to recognize the allelic variation. A trinucleotide deletion (c.4_6delAGG) was identified in the first exon ofMTRR. All the three women showed the novel clinical variation including one heterozygous and two homozygous. The s...
Source: NeuroMolecular Medicine - July 15, 2017 Category: Neurology Source Type: research

Transgenic Mice Overexpressing the Divalent Metal Transporter 1 Exhibit Iron Accumulation and Enhanced Parkin Expression in the Brain
AbstractExposure to divalent metals such as iron and manganese is thought to increase the risk for Parkinson ’s disease (PD). Under normal circumstances, cellular iron and manganese uptake is regulated by the divalent metal transporter 1 (DMT1). Accordingly, alterations in DMT1 levels may underlie the abnormal accumulation of metal ions and thereby disease pathogenesis. Here, we have generated transgenic mice overexpressing DMT1 under the direction of a mouse prion promoter and demonstrated its robust expression in several regions of the brain. When fed with iron-supplemented diet, DMT1-expressing mice exhibit rather...
Source: NeuroMolecular Medicine - July 10, 2017 Category: Neurology Source Type: research

Vitamin D 3 Reverses the Hippocampal Cytoskeleton Imbalance But Not Memory Deficits Caused by Ovariectomy in Adult Wistar Rats
The objective of study was to investigate changes caused by ovariectomy (OVX) on aversive and non-aversive memories, as well as on cytoskeleton phosphorylating system and on vitamin D receptor (VDR) immunocontent in hippocampus. The neuroprotective role of vitamin D was also investigated. Ninety-day-old female Wistar rats were divided into four groups: SHAM, OVX, VITAMIN D and OVX  + VITAMIN D; 30 days after the OVX, vitamin D supplementation (500 IU/kg), by gavage, for 30 days was started. Results showed that OVX impaired short-term and long-term recognition, and long-term aversive memories. OVX a...
Source: NeuroMolecular Medicine - July 8, 2017 Category: Neurology Source Type: research

Functional and Molecular Characterization of a Novel Traumatic Peripheral Nerve –Muscle Injury Model
AbstractTraumatic injuries to human peripheral nerves are frequently associated with damage to nerve surrounding tissues including muscles and blood vessels. Currently, most rodent models of peripheral nerve injuries (e.g., facial or sciatic nerve) employ surgical nerve transection with scissors or scalpels. However, such an isolated surgical nerve injury only mildly damages neighboring tissues and weakly activates an immune response. In order to provide a rodent nerve injury model accounting for such nerve-associated tissue damage and immune cell activation, we developed a drop tower-based facial nerve trauma model in mic...
Source: NeuroMolecular Medicine - July 8, 2017 Category: Neurology Source Type: research

Deferiprone Rescues Behavioral Deficits Induced by Mild Iron Exposure in a Mouse Model of Alpha-Synuclein Aggregation
AbstractParkinson ’s disease (PD) is the most common neurodegenerative movement disorder, and its causes remain unknown. A major hallmark of the disease is the increasing presence of aggregated alpha-synuclein (aSyn). Furthermore, there is a solid consensus on iron (Fe) accumulation in several regions of PD brains during disease progression. In our study, we focused on the interaction of Fe and aggregating aSyn in vivo in a transgenic mouse model overexpressing human aSyn bearing the A53T mutation (prnp.aSyn.A53T). We utilized a neonatal iron-feeding model to exacerbate the motor phenotype of the transgenic m ouse mo...
Source: NeuroMolecular Medicine - June 16, 2017 Category: Neurology Source Type: research

Individual Amino Acid Supplementation Can Improve Energy Metabolism and Decrease ROS Production in Neuronal Cells Overexpressing Alpha-Synuclein
AbstractParkinson ’s disease (PD) is a neurodegenerative disorder characterized by alpha-synuclein accumulation and loss of dopaminergic neurons in the substantia nigra (SN) region of the brain. Increased levels of alpha-synuclein have been shown to result in loss of mitochondrial electron transport chain complex I activity leading to increased reactive oxygen species (ROS) production. WT alpha-synuclein was stably overexpressed in human BE(2)-M17 neuroblastoma cells resulting in increased levels of an alpha-synuclein multimer, but no increase in alpha-synuclein monomer levels. Oxygen consumption was decrease d by al...
Source: NeuroMolecular Medicine - June 15, 2017 Category: Neurology Source Type: research

Invaginating Presynaptic Terminals in Neuromuscular Junctions, Photoreceptor Terminals, and Other Synapses of Animals
AbstractTypically, presynaptic terminals form a synapse directly on the surface of postsynaptic processes such as dendrite shafts and spines. However, some presynaptic terminals invaginate —entirely or partially—into postsynaptic processes. We survey these invaginating presynaptic terminals in all animals and describe several examples from the central nervous system, including giant fiber systems in invertebrates, and cup-shaped spines, electroreceptor synapses, and some specializ ed auditory and vestibular nerve terminals in vertebrates. We then examine mechanoreceptors and photoreceptors, concentrating on the...
Source: NeuroMolecular Medicine - June 13, 2017 Category: Neurology Source Type: research

Low-Density Lipoprotein Receptor-Related Protein-1 (LRP1) C4408R Mutant Promotes Amyloid Precursor Protein (APP) α-Cleavage in Vitro
AbstractPrevious studies have demonstrated that the low-density lipoprotein receptor-related protein-1 (LRP1) plays conflicting roles in Alzheimer ’s disease (AD) pathogenesis, clearing β-amyloid (Aβ) from the brain while also enhancing APP endocytosis and resultant amyloidogenic processing. We have recently discovered that co-expression of mutant LRP1 C-terminal domain (LRP1-CT C4408R) with Swedish mutant amyloid precursor protein (APPswe ) in Chinese hamster ovary (CHO) cells decreases Aβ production, while also increasing sAPPα and APP α-C-terminal fragment (α-CTF), compared with CH...
Source: NeuroMolecular Medicine - June 13, 2017 Category: Neurology Source Type: research

rs3851179 Polymorphism at 5 ′ to the PICALM Gene is Associated with Alzheimer and Parkinson Diseases in Brazilian Population
AbstractAlzheimer ’s (AD) and Parkinson’s diseases (PD) share clinical and pathological features, suggesting that they could have common pathogenic mechanisms, as well as overlapping genetic modifiers. Here, we performed a case–control study in a Brazilian population to clarify whether the risk of AD and PD mig ht be influenced by shared polymorphisms atPICALM (rs3851179),CR1 (rs6656401) andCLU (rs11136000) genes, which were previously identified as AD risk factors by genome-wide association studies. For this purpose, 174 late-onset AD patients, 166 PD patients and 176 matched controls were genotyped usin...
Source: NeuroMolecular Medicine - May 31, 2017 Category: Neurology Source Type: research

Models for Studying Myelination, Demyelination and Remyelination
AbstractOne of the most widely studied demyelinating diseases is multiple sclerosis, which is characterised by the appearance of demyelinating plaques, followed by myelin regeneration. Nevertheless, with disease progression, remyelination tends to fail, increasing the characteristic neurodegeneration of the disease. It is essential to understand the mechanisms that operate in the processes of myelination, demyelination and remyelination to develop treatments that promote the production of new myelin, thereby protecting the central nervous system. A huge variety of models have been developed to help improve our understandin...
Source: NeuroMolecular Medicine - May 23, 2017 Category: Neurology Source Type: research

PLXNA3 Variant rs5945430 is Associated with Severe Clinical Course in Male Multiple Sclerosis Patients
AbstractMultiple sclerosis (MS) exhibits sex bias in disease clinical course as male MS patients develop severe, progressive clinical course with accumulating disability. So far, no factors have been found associating with this sex bias in MS severity. We set out to determine the genetic factor contributing to MS male-specific progressive disease. This is an MS cross-sectional study involving 213 Kuwaiti MS patients recruited at Dasman Diabetes Institute. Exome sequencing was performed on 18 females and 8 male MS patients ’ genomic DNA. rs5945430 genotyping was performed using Taqman genotyping assay. Estradiol level...
Source: NeuroMolecular Medicine - May 23, 2017 Category: Neurology Source Type: research

Assessment of the Neuroprotective Effects of Arginine-Rich Protamine Peptides, Poly-Arginine Peptides (R12-Cyclic, R22) and Arginine –Tryptophan-Containing Peptides Following In Vitro Excitotoxicity and/or Permanent Middle Cerebral Artery Occlusion in Rats
AbstractWe have demonstrated that arginine-rich and poly-arginine peptides possess potent neuroprotective properties with arginine content and peptide positive charge being particularly critical for neuroprotective efficacy. In addition, the presence of other amino acids within arginine-rich peptides, as well as chemical modifications, peptide length and cell-penetrating properties also influence the level of neuroprotection. Against this background, we have examined the neuroprotective efficacy of arginine-rich protamine peptides, a cyclic (R12-c) poly-arginine peptide and a R22 poly-arginine peptide, as well as arginine ...
Source: NeuroMolecular Medicine - May 18, 2017 Category: Neurology Source Type: research

Mild TBI Results in a Long-Term Decrease in Circulating Phospholipids in a Mouse Model of Injury
We examined long-term plasma phospholipid profiles in a mouse model of mTBI to determine their translational value in re producing PL changes observed in mTBI patients. Plasma samples were collected at an acute timepoint (24 h post-injury) and at several chronic stages (3, 6, 12 and 24 months post-injury) from injured mice and sham controls. Phospholipids were identified and quantified using liquid chromatography/ma ss spectrometry analysis. In accordance with human data, we observed significantly lower levels of several major PL classes in mTBI mice compared to controls at chronic timepoints. Saturated, monounsa...
Source: NeuroMolecular Medicine - March 1, 2017 Category: Neurology Source Type: research

Antidepressant-Like and Anxiolytic-Like Effects of ZBD-2, a Novel Ligand for the Translocator Protein (18  kDa)
AbstractActivation of translocator protein (18  kDa) (TSPO) plays an important role to mediate rapid anxiolytic efficacy in stress response and stress-related disorders by the production of neurosteroids. However, little is known about the ligand of TSPO on the anxiety-like and depressive behaviors and the underlying mechanisms in chronic unpre dictable mild stress (UCMS) mice. In the present study, a novel ligand of TSPO, ZBD-2 [N-benzyl-N-ethyl-2-(7,8-dihydro-7-benzyl-8-oxo-2-phenyl-9H-purin-9-yl) acetamide] synthesized by our laboratory, was used to evaluate the anxiolytic and antidepressant efficacy and to elucida...
Source: NeuroMolecular Medicine - March 1, 2017 Category: Neurology Source Type: research

The Effects of Alpha Boswellic Acid on Reelin Expression and Tau Phosphorylation in Human Astrocytes
AbstractReelin is an extracellular glycoprotein which contributes to synaptic plasticity and function of memory in the adult brain. It has been indicated that the Reelin signaling cascade participates in Alzheimer ’s disease (AD). Besides the neurons, glial cells such as astrocytes also express Reelin protein. While functional loss of astrocytes has been reported to be associated with AD, dysfunction of astrocytic Reelin signaling pathway has not received much attention. Therefore, we investigated the effec ts of α-boswellic acid (ABA) as one of the major component ofBoswellia serrata resin on primary fetal hum...
Source: NeuroMolecular Medicine - March 1, 2017 Category: Neurology Source Type: research

Parthenolide, an NF- κB Inhibitor Ameliorates Diabetes-Induced Behavioural Deficit, Neurotransmitter Imbalance and Neuroinflammation in Type 2 Diabetes Rat Model
AbstractDiabetes is associated with behavioural and neurochemical alterations. In this manuscript, we are reporting the beneficial effects of parthenolide, an NF- κB inhibitor on behavioural and neurochemical deficits in type 2 diabetic rat model. Diabetes was induced by high-fat diet followed by low dose of streptozotocin (35 mg/kg). Elevated plus maze, open-field, MWM and passive avoidance test paradigm were used to assess behavioural and cognitive defici ts. Three-week treatment of parthenolide (0.25 and 0.50 mg/kg;i.p.) attenuated diabetes-induced alteration in cognitive function in Morris water maze an...
Source: NeuroMolecular Medicine - March 1, 2017 Category: Neurology Source Type: research

Association of GWAS-Supported Variants rs556621 on Chromosome 6p21.1 with Large Artery Atherosclerotic Stroke in a Southern Chinese Han Population
This study aimed to evaluate whether rs556621 was associated with LAA stroke in Chinese Han population. In this case –control study, 659 patients with LAA stroke and 650 healthy controls were enrolled. Associations between rs556621 genotypes and LAA stroke were analyzed with logistic regression model. Rs556621 variants were associated with increased risks of LAA stroke (codominant model: OR 1.42; 95 % CI 1.01– 1.99;P = 0.010; recessive model: OR 1.40; 95 % CI 1.05–1.86;P = 0.003). When subjects were stratified by sex, TT genotype of SNP rs556621 was associated with an increas...
Source: NeuroMolecular Medicine - March 1, 2017 Category: Neurology Source Type: research

Mutant A53T α-Synuclein Improves Rotarod Performance Before Motor Deficits and Affects Metabolic Pathways
AbstractThe protein α-synuclein (α-Syn) interferes with glucose and lipid uptake and also activates innate immune cells. However, it remains unclear whether α-Syn or its familial mutant forms contribute to metabolic alterations and inflammation in synucleinopathies, such as Parkinson’s disease (PD). Here, we addre ss this issue in transgenic mice for the mutant A53T human α-Syn (α-SynA53T), a mouse model of synucleinopathies. At 9.5 months of age, mice overexpressing α-SynA53T (homozygous) had a significant reduction in weight, exhibited improved locomotion and did not show ma...
Source: NeuroMolecular Medicine - March 1, 2017 Category: Neurology Source Type: research

Molecular and Functional Characterization of a Cohort of Spanish Patients with Ataxia-Telangiectasia
AbstractAtaxia-telangiectasia is a multisystemic disease with severe neurological affectation, immunodeficiency and telangiectasia. The disorder is caused by alterations in theATM gene, whose size and complexity make molecular diagnosis difficult. We designed a target-enrichment next-generation sequencing strategy to characterize 28 patients from several regions of Spain. This approach allowed us to identify gene variants affecting function in 54 out of the 56 alleles analyzed, although the two unresolved alleles belong to brothers. We found 28ATM gene mutations, of which 10 have not been reported. A total of 171 gene vari...
Source: NeuroMolecular Medicine - September 23, 2016 Category: Neurology Source Type: research

Cerebrospinal Fluid Stanniocalcin-1 as a Biomarker for Alzheimer ’s Disease and Other Neurodegenerative Disorders
AbstractStanniocalcin-1 (STC-1) is a nerve cell-enriched protein involved in intracellular calcium homeostasis regulation. Changes in calcium regulation are hypothesized to play a role in the pathophysiology of Alzheimer ’s disease (AD). The expression of STC-1 increases in response to ischemic stroke, but whether it is altered in neurodegenerative disorder, particularly Alzheimer’s disease (AD), has not been investigated before. We measured STC-1 in cerebrospinal fluid (CSF) samples from a total of 163 individu als including AD, prodromal AD (pAD), mixed AD, stable mild cognitive impairment (sMCI), and diagnos...
Source: NeuroMolecular Medicine - September 19, 2016 Category: Neurology Source Type: research

Pro198Leu Polymorphism in the Glutathione Peroxidase 1 Gene Contributes to Diabetic Peripheral Neuropathy in Type 2 Diabetes Patients
In conclusion, our findin gs suggest that Gpx1 Pro198Leu genotypes are significantly associated with the risk of diabetic peripheral neuropathy in patients with T2DM. The study provides new clinically relevant information regarding genetic determinants of susceptibility to diabetic neuropathy. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - September 3, 2016 Category: Neurology Source Type: research

Nutraceuticals in Parkinson ’s Disease
AbstractCurrent 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. Nutraceut icals 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 position themse...
Source: NeuroMolecular Medicine - August 14, 2016 Category: Neurology Source Type: research

Nutraceuticals in Neurodegeneration and Aging
(Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - August 9, 2016 Category: Neurology Source Type: research

Identification of Novel SCIRR69-Interacting Proteins During ER Stress Using SILAC-Immunoprecipitation Quantitative Proteomics Approach
In this study, we firstly treated fetal rat spinal cord neuron cells (SCN) and PC12 cells with ER stress activator thapsigargin (TG) or tunicamycin (TM) and then detected the expression pattern of SCIRR69 in response to ER stress at mRNA and protein levels using real-time PCR assay and immunoblotting. Results showed that the expression pattern of SCIRR69 was largely consistent with those of ER stress marker (ATF6, BIP and CHOP) at either mRNA level or protein level, implying that SCIRR69 may play important roles in ER stress. Subsequently, we used stable isotope labeling by amino acids in cell culture (SILAC)-immunoprecipi...
Source: NeuroMolecular Medicine - August 3, 2016 Category: Neurology Source Type: research

Integrins AV and B8 Gene Polymorphisms and Risk for Intracerebral Hemorrhage in Greek and Polish Populations
Abstract Α limited number of genetic variants have been linked to the development of intracerebral hemorrhage (ICH). Ιntegrin AV and/or B8-deficient mice were found to develop ICH. The present candidate gene association study was designed to investigate possible influence of integrin AV (ITGAV) and integri n B8 (ITGB8) gene region polymorphisms on the risk of ICH. 1015 participants (250 Greek and 193 Polish patients with primary ICH and 250 Greek and 322 Polish controls) were included in the study. Using logistic regression analyses, 11 tag single nucleotide polymorphisms (SNPs) for ITGAV and 11 for I TGB8 gene...
Source: NeuroMolecular Medicine - July 30, 2016 Category: Neurology Source Type: research

Role of dietary phenols in mitigating microglia-mediated neuroinflammation
Abstract Chronic neuroinflammation is a pathological feature of a number of central nervous system (CNS) diseases and is mediated by sustained activation of microglial cells, the innate immune cells of the CNS. Studies have mainly focused on identifying the molecular and epigenetic mechanisms of microglial activation. This is crucial in designing therapeutic strategies for neuropathologies in which prolonged microglial activation is known to exacerbate disease condition. In recent years, increasing evidence show that naturally occurring compounds present in regular diet could function as “nutraceuticals,” arre...
Source: NeuroMolecular Medicine - July 27, 2016 Category: Neurology Source Type: research

Effects of Grape Skin Extract on Age-Related Mitochondrial Dysfunction, Memory and Life Span in C57BL/6J Mice
This study aimed to investigate the effects of a polyphenol-rich grape skin extract (PGE) on age-re lated dysfunctions of brain mitochondria, memory, life span and potential hormetic pathways in C57BL/6J mice. PGE was administered at a dose of 200 mg/kg body weight/d in a 3-week short-term, 6-month long-term and life-long study. MD in the brains of aged mice (19–22 months old) compared to youn g mice (3 months old) was demonstrated by lower ATP levels and by impaired mitochondrial respiratory complex activity (except for mice treated with antioxidant-depleted food pellets). Long-term PGE feeding p...
Source: NeuroMolecular Medicine - July 25, 2016 Category: Neurology Source Type: research

Erratum to: GC and VDR SNPs and Vitamin D Levels in Parkinson ’s Disease: The Relevance to Clinical Features
(Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - July 21, 2016 Category: Neurology Source Type: research

Neuroprotective Effects of Germinated Brown Rice in Rotenone-Induced Parkinson ’s-Like Disease Rats
In this study, 4-phenylbutyric acid (4-PBA), previously reported to inhibit RT-induced DA cell death, was used as the positive control. Results show that pretreatment with GBR as well as 4-PBA significantly enhanced the motor activity after RT injection, and GBR affected significantly in open field test, only in the ambulation b ut not the mobility duration, and ameliorated the time to orient down (t-turn) and total time to descend the pole (t-total) in pole test as compared to RT group, but significantly lowered both t-turn and t-total only in 4-PBA group. The percentage of apoptotic cells in brain measured by flow cytome...
Source: NeuroMolecular Medicine - July 18, 2016 Category: Neurology Source Type: research

Neuroprotective Effects of Germinated Brown Rice in Rotenone-Induced Parkinson’s-Like Disease Rats
In this study, 4-phenylbutyric acid (4-PBA), previously reported to inhibit RT-induced DA cell death, was used as the positive control. Results show that pretreatment with GBR as well as 4-PBA significantly enhanced the motor activity after RT injection, and GBR affected significantly in open field test, only in the ambulation but not the mobility duration, and ameliorated the time to orient down (t-turn) and total time to descend the pole (t-total) in pole test as compared to RT group, but significantly lowered both t-turn and t-total only in 4-PBA group. The percentage of apoptotic cells in brain measured by flow cytomet...
Source: NeuroMolecular Medicine - July 18, 2016 Category: Neurology Source Type: research

Biological Effects of Naturally Occurring Sphingolipids, Uncommon Variants, and Their Analogs
Abstract Sphingolipids (SPs) comprise a highly diverse class of lipids that serve biological roles both as structural components of cell membranes and as mediators of cell signaling. Pharmacologic and genetic manipulation of SPs and their signaling systems have underscored their importance in most biological processes, including central nervous system development and function. Likewise, perturbations of SP accumulation or signaling have been associated with a number of disease states, such as neural tube defects, neuroinflammation, stroke, and dementia. SPs can be endogenously synthesized de novo, and their metabo...
Source: NeuroMolecular Medicine - July 8, 2016 Category: Neurology Source Type: research

Increased Plasma Levels of Select Deoxy-ceramide and Ceramide Species are Associated with Increased Odds of Diabetic Neuropathy in Type 1 Diabetes: A Pilot Study
Abstract Plasma deoxy-sphingoid bases are elevated in type 2 diabetes patients and correlate with the stage of diabetic distal sensorimotor polyneuropathy; however, associations between deoxy-sphingolipids (DSL) and neuropathy in type 1 diabetes have not been examined. The primary aim of this exploratory pilot study was to assess the associations between multiple sphingolipid species including DSL and free amino acids and the presence of symptomatic neuropathy in a DCCT/EDIC type 1 diabetes subcohort. Using mass spectroscopy, plasma levels of DSL and free amino acids in DCCT/EDIC type 1 diabetes participants (n&nb...
Source: NeuroMolecular Medicine - July 7, 2016 Category: Neurology Source Type: research

Epigenetic Modifications and Therapy in Multiple Sclerosis
Abstract Breakthroughs in genetic studies, like whole human genome sequencing and genome-wide association studies (GWAS), have richened our knowledge of etiopathology of autoimmune diseases (AID) through discovery of genetic patterns. Nonetheless, the precise etiology of autoimmune diseases remains largely unknown. The lack of complete concordance of autoimmune disease in identical twins suggests that non-genetic factors also play a major role in determining disease susceptibility. Although there is no certain definition, epigenetics has been known as heritable alterations in gene function without changes in the n...
Source: NeuroMolecular Medicine - July 6, 2016 Category: Neurology Source Type: research

Choline Ameliorates Disease Phenotypes in Human iPSC Models of Rett Syndrome
Abstract Rett syndrome (RTT) is a postnatal neurodevelopmental disorder that primarily affects girls. Mutations in the methyl-CpG-binding protein 2 (MECP2) gene account for approximately 95 % of all RTT cases. To model RTT in vitro, we generated induced pluripotent stem cells (iPSCs) from fibroblasts of two RTT patients with different mutations (MECP2 R306C and MECP2 1155Δ32) in their MECP2 gene. We found that these iPSCs were capable of differentiating into functional neurons. Compared to control neurons, the RTT iPSC-derived cells had reduced soma size and a decreased amoun...
Source: NeuroMolecular Medicine - July 5, 2016 Category: Neurology Source Type: research

Effects of Long-Term Rice Bran Extract Supplementation on Survival, Cognition and Brain Mitochondrial Function in Aged NMRI Mice
Abstract Aging represents a major risk factor for the development of neurodegenerative diseases like Alzheimer’s disease (AD). As mitochondrial dysfunction plays an important role in brain aging and occurs early in the development of AD, the prevention of mitochondrial dysfunction might help to slow brain aging and the development of neurodegenerative diseases. Rice bran extract (RBE) contains high concentrations of vitamin E congeners and γ-oryzanol. We have previously shown that RBE increased mitochondrial function and protected from mitochondrial dysfunction in vitro and in short-term in vivo feedin...
Source: NeuroMolecular Medicine - June 27, 2016 Category: Neurology Source Type: research

Recommendations for Development of Botanical Polyphenols as “Natural Drugs” for Promotion of Resilience Against Stress-Induced Depression and Cognitive Impairment
Abstract Extensive evidence has demonstrated that psychological stress has detrimental effects on psychological health, cognitive function, and ultimately well-being. While stressful events are a significant cause of psychopathology, most individuals exposed to adversity maintain normal psychological functioning. The mechanisms underlying such resilience are poorly understood, and there is an urgent need to identify and target these mechanisms to promote resilience under stressful events. Botanicals have been used throughout history to treat various medical conditions; however, the development of botanical compoun...
Source: NeuroMolecular Medicine - June 24, 2016 Category: Neurology Source Type: research