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

Up-Regulation of Neuronal Nitric Oxide Synthase Expression by Cobalt Chloride Through a HIF-1α Mechanism in Neuroblastoma Cells
Abstract Nitric oxide (NO) plays a dual role in response to neural hypoxia. NO is synthesized by three isoforms of nitric oxide synthase (NOS), among which the neuronal NOS (nNOS) is predominant in the nervous system. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that is induced under hypoxic conditions, but its correlation with nNOS remains unclear. In the present study, we aimed at clarifying the regulation pattern of the nNOS expression in response to cobalt chloride (CoCl2), a widely used chemical mimic of hypoxia, and the role of HIF-1α in this process in neuroblastoma c...
Source: NeuroMolecular Medicine - October 12, 2015 Category: Neurology Source Type: research

Low-Dose DMC Significantly Enhances the Effect of TMZ on Glioma Cells by Targeting Multiple Signaling Pathways Both In Vivo and In Vitro
In this study, we found low-dose demethoxycurcumin (DMC) could enhance the sensitivity of TMZ on glioma cells, and high-dose DMC has more significant effects on GBM cells compared with TMZ treatment alone both in vitro and in vivo. And co-administration of DMC and TMZ resulted in a significant increase in GBM apoptosis and a marked inhibition of cell growth pathogenesis of GBM. Mechanistically, DMC and TMZ synergistically increase intracellular level of reactive oxygen species (ROS) production, activate caspase-3-dependent apoptotic pathway, and inactivate of JAK/STAT3 signaling pathway in GBMs, which account for the cell ...
Source: NeuroMolecular Medicine - October 12, 2015 Category: Neurology Source Type: research

Association Study of CHRNA7 Promoter Variants with Sensory and Sensorimotor Gating in Schizophrenia Patients and Healthy Controls: A Danish Case–Control Study
In this study, 95 antipsychotic-naïve schizophrenic patients and 450 unaffected controls were screened for CHRNA7 promoter variants to investigate the association with schizophrenia, P50 suppression and PPI. We found that the promoter variant -194C (rs28531779) was significantly associated with schizophrenia, but did not find any association of this variant with P50 suppression or PPI. In addition, individuals with CHRNA7 promoter variants had elevated startle magnitude in pulse-alone trials compared to individuals without a variant. The present findings provide further support for a role of the α7nAChR in schiz...
Source: NeuroMolecular Medicine - September 16, 2015 Category: Neurology Source Type: research

Current Neurogenic and Neuroprotective Strategies to Prevent and Treat Neurodegenerative and Neuropsychiatric Disorders
Abstract The adult central nervous system is commonly known to have a very limited regenerative capacity. The presence of functional stem cells in the brain can therefore be seen as a paradox, since in other organs these are known to counterbalance cell loss derived from pathological conditions. This fact has therefore raised the possibility to stimulate neural stem cell differentiation and proliferation or survival by either stem cell replacement therapy or direct administration of neurotrophic factors or other proneurogenic molecules, which in turn has also originated regenerative medicine for the treatment of o...
Source: NeuroMolecular Medicine - September 15, 2015 Category: Neurology Source Type: research

Matrix Metalloproteinase-9 (MMP-9) Gene Polymorphism in Stroke Patients
In conclusion, our findings suggest that MMP-9 C(-1562)T polymorphism is significantly associated with risk of stroke in patients with and without T2DM. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - September 1, 2015 Category: Neurology Source Type: research

Roles of Treg/Th17 Cell Imbalance and Neuronal Damage in the Visual Dysfunction Observed in Experimental Autoimmune Optic Neuritis Chronologically
Abstract Optic neuritis associated with multiple sclerosis and its animal model, experimental autoimmune optic neuritis (EAON), is characterized by inflammation, T cell activation, demyelination, and neuronal damage, which might induce permanent vision loss. Elucidating the chronological relationship among the features is critical for treatment of demyelinating optic neuritis. EAON was induced in C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein subcutaneously, and visual function was assessed by flash-visual evoked potential (F-VEP) at days 7, 11, 14, 19, 23, 28 post-immunization. Retinal ganglion c...
Source: NeuroMolecular Medicine - August 30, 2015 Category: Neurology Source Type: research

Rho GTPase RAC1 at the Molecular Interface Between Genetic and Environmental Factors of Autism Spectrum Disorders
(Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - August 25, 2015 Category: Neurology Source Type: research

Systematic Review by Multivariate Meta-analyses on the Possible Role of Tumor Necrosis Factor-α Gene Polymorphisms in Association with Ischemic Stroke
In conclusion, the present systematic review and meta-analysis support a prominent role of the TNF-α −238G/A polymorphism in the risk of ischemic stroke in Asian adults only, but do not support the role of −308G/A, −857C/T, −1031T/C, −244G/A, −367G/A, −646G/A, −806C/T, −863C/A, and +448G/A in the risk of ischemic stroke. The current evidence warrants further studies with high quality and large sample size to confirm. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - July 31, 2015 Category: Neurology Source Type: research

The Dynamics of Interactions Among Immune and Glioblastoma Cells
Abstract Glioblastoma is the most common intracranial malignancy that constitutes about 50 % of all gliomas. Despite aggressive, multimodal therapy consisting of surgery, radiation, and chemotherapy, the outcome of patients with glioblastoma remains poor with 5-year survival rates of
Source: NeuroMolecular Medicine - July 30, 2015 Category: Neurology Source Type: research

Role of Oxidative Stress in the Worsening of Neurologic Wilson Disease Following Chelating Therapy
We report the role of plasma glutathione (GSH), total antioxidant capacity (TAC) and malondialdehyde (MDA) in the worsening of NWD following treatment. Fifty-one treatment-naïve NWD patients were subjected to detailed clinical evaluation. The severity of NWD was noted, and dystonia was measured by Burke–Fahn–Marsden (BFM) score. Their hematological, serum chemistry, ultrasound abdomen and cranial MRI changes were noted. Plasma GSH, TAC and MDA, serum free copper (Cu) and 24-h urinary Cu were measured at admission and at 3 and 6 months after treatment. The patients were considered worsened if there was...
Source: NeuroMolecular Medicine - July 29, 2015 Category: Neurology Source Type: research

Astrocyte Transcriptome from the Mecp2 308 -Truncated Mouse Model of Rett Syndrome
Abstract Mutations in the gene encoding the transcriptional modulator methyl-CpG binding protein 2 (MeCP2) are responsible for the neurodevelopmental disorder Rett syndrome which is one of the most frequent sources of intellectual disability in women. Recent studies showed that loss of Mecp2 in astrocytes contributes to Rett-like symptoms and restoration of Mecp2 can rescue some of these defects. The goal of this work is to compare gene expression profiles of wild-type and mutant astrocytes from Mecp2308/y mice (B6.129S-MeCP2/J) by using Affymetrix mouse 2.0 microarrays. Results were confirmed by quantitative ...
Source: NeuroMolecular Medicine - July 25, 2015 Category: Neurology Source Type: research

Lower Cerebrospinal Fluid Concentration of Brain-Derived Neurotrophic Factor Predicts Progression from Mild Cognitive Impairment to Alzheimer’s Disease
Abstract There is little information on the dynamics of BDNF in the CSF in the continuum between healthy aging, MCI and AD. We included 128 older adults (77 with amnestic MCI, 26 with AD and 25 healthy controls). CSF BDNF level was measured by ELISA assay, and AD biomarkers (Aβ42, T-Tau and P-Tau181) were measured using a Luminex xMAP assay. CSF BDNF levels were significantly reduced in AD subjects compared to MCI and healthy controls (p = 0.009). Logistic regression models showed that lower CSF BDNF levels (p = 0.008), lower CSF Aβ42 (p = 0.005) and lower MMSE scores (p&nbs...
Source: NeuroMolecular Medicine - July 3, 2015 Category: Neurology Source Type: research

NGF Expression in Reelin-Deprived Retinal Cells: A Potential Neuroprotective Effect
Abstract We recently reported that increased NGF and p75NTR as well as decreased trkANGFR characterized the Reelin-deprived (E-Reeler) retina, prospecting a potential contribution of NGF during E-Reeler retinogenesis. Herein, retinal ganglion cells (RGCs), glial cells and rod bipolar cells (RBCs) were isolated from E-Reeler retinas, and NGF, trkANGFR/p75NTR expression and apoptosis were investigated. E-Reeler (n = 28) and E-control (n = 34) retinas were digested, and RGCs, glial cells and RBCs were isolated by the magnetic bead separation. Expression of NGF, trkANGFR, p75NTR, Annexin V/PI and B...
Source: NeuroMolecular Medicine - June 12, 2015 Category: Neurology Source Type: research

Restoration of Normal Cerebral Oxygen Consumption with Rapamycin Treatment in a Rat Model of Autism–Tuberous Sclerosis
Abstract Tuberous sclerosis (TSC) is associated with autism spectrum disorders and has been linked to metabolic dysfunction and unrestrained signaling of the mammalian target of rapamycin (mTOR). Inhibition of mTOR by rapamycin can mitigate some of the phenotypic abnormalities associated with TSC and autism, but whether this is due to the mTOR-related function in energy metabolism remains to be elucidated. In young Eker rats, an animal model of TSC and autism, which harbors a germ line heterozygous Tsc2 mutation, we previously reported that cerebral oxygen consumption was pronouncedly elevated. Young (4 weeks...
Source: NeuroMolecular Medicine - June 6, 2015 Category: Neurology Source Type: research

Clinical, Molecular, and Functional Characterization of CLCN1 Mutations in Three Families with Recessive Myotonia Congenita
Abstract Myotonia congenita (MC) is an inherited muscle disease characterized by impaired muscle relaxation after contraction, resulting in muscle stiffness. Both recessive (Becker’s disease) or dominant (Thomsen’s disease) MC are caused by mutations in the CLCN1 gene encoding the voltage-dependent chloride ClC-1 channel, which is quite exclusively expressed in skeletal muscle. More than 200 CLCN1 mutations have been associated with MC. We provide herein a detailed clinical, molecular, and functional evaluation of four patients with recessive MC belonging to three different families. Four CLCN1 variant...
Source: NeuroMolecular Medicine - May 26, 2015 Category: Neurology Source Type: research

Structure, Distribution, and Function of Neuronal/Synaptic Spinules and Related Invaginating Projections
Abstract Neurons and especially their synapses often project long thin processes that can invaginate neighboring neuronal or glial cells. These “invaginating projections” can occur in almost any combination of postsynaptic, presynaptic, and glial processes. Invaginating projections provide a precise mechanism for one neuron to communicate or exchange material exclusively at a highly localized site on another neuron, e.g., to regulate synaptic plasticity. The best-known types are postsynaptic projections called “spinules” that invaginate into presynaptic terminals. Spinules seem to be most p...
Source: NeuroMolecular Medicine - May 26, 2015 Category: Neurology Source Type: research

Are Molecules Involved in Neuritogenesis and Axon Guidance Related to Autism Pathogenesis?
Abstract Autism spectrum disorder is a heterogeneous disease, and numerous alterations of gene expression come into play to attempt to explain potential molecular and pathophysiological causes. Abnormalities of brain development and connectivity associated with alterations in cytoskeletal rearrangement, neuritogenesis and elongation of axons and dendrites might represent or contribute to the structural basis of autism pathology. Slit/Robo signaling regulates cytoskeletal remodeling related to axonal and dendritic branching. Components of its signaling pathway (ABL and Cdc42) are suspected to be molecular bases...
Source: NeuroMolecular Medicine - May 20, 2015 Category: Neurology Source Type: research

Epigenetics of Multiple Sclerosis: An Updated Review
Abstract Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease characterized with autoimmune response against myelin proteins and progressive axonal loss. The heterogeneity of the clinical course and low concordance rates in monozygotic twins have indicated the involvement of complex heritable and environmental factors in MS pathogenesis. MS is more often transmitted to the next generation by mothers than fathers suggesting an epigenetic influence. One of the possible reasons of this parent-of-origin effect might be the human leukocyte antigen-DRB1*15 allele, which is the major risk factor for ...
Source: NeuroMolecular Medicine - May 7, 2015 Category: Neurology Source Type: research

Epigenetic Regulation of Memory by Acetylation and Methylation of Chromatin: Implications in Neurological Disorders, Aging, and Addiction
Abstract Synaptic plasticity is one of the most fundamental properties of neurons that underlie the formation of the memory in brain. In recent years, epigenetic modification of both DNA and histones such as DNA methylation and histone acetylation and methylation emerges as a potential regulatory mechanism that governs the transcription of several genes responsible for memory formation and behavior. Furthermore, the recent identification of nitrosylation of proteins has shown to either activate or repress gene transcription by modulating histone methylation or acetylation status in mature neuron. Recent studi...
Source: NeuroMolecular Medicine - May 7, 2015 Category: Neurology Source Type: research

Alpha-Linolenic Acid-Induced Increase in Neurogenesis is a Key Factor in the Improvement in the Passive Avoidance Task After Soman Exposure
Abstract Exposure to organophosphorous (OP) nerve agents such as soman inhibits the critical enzyme acetylcholinesterase (AChE) leading to excessive acetylcholine accumulation in synapses, resulting in cholinergic crisis, status epilepticus and brain damage in survivors. The hippocampus is profoundly damaged after soman exposure leading to long-term memory deficits. We have previously shown that treatment with three sequential doses of alpha-linolenic acid, an essential omega-3 polyunsaturated fatty acid, increases brain plasticity in naïve animals. However, the effects of this dosing schedule administere...
Source: NeuroMolecular Medicine - April 29, 2015 Category: Neurology Source Type: research

Neuronal Network Oscillations in Neurodegenerative Diseases
Abstract Cognitive and behavioral acts go along with highly coordinated spatiotemporal activity patterns in neuronal networks. Most of these patterns are synchronized by coherent membrane potential oscillations within and between local networks. By entraining multiple neurons into a common time regime, such network oscillations form a critical interface between cellular activity and large-scale systemic functions. Synaptic integrity is altered in neurodegenerative diseases, and it is likely that this goes along with characteristic changes of coordinated network activity. This notion is supported by EEG recordi...
Source: NeuroMolecular Medicine - April 29, 2015 Category: Neurology Source Type: research

KALRN Rare and Common Variants and Susceptibility to Ischemic Stroke in Chinese Han Population
In this study, we analyzed four KALRN gene SNPs in 503 ischemic stroke patients and 493 control subjects, separating the patients into separate research groups based on comorbidity with hypertension or diabetes and stroke type (atherosis or lacunar and combination type). We found a rare variant of KALRN, rs11712619, that associated with lacunar stroke in the northern Chinese Han population with an average-risk allele frequency 0.009 (OR 2.95, 95 % CI 1.08–8.01, p = 0.028). However, after adjusting for relevant factors, including sex, age, body mass index, dyslipidemia, alcohol consumption, and smoking,...
Source: NeuroMolecular Medicine - April 28, 2015 Category: Neurology Source Type: research

TSC1 R509X Mutation in a Chinese Family with Tuberous Sclerosis Complex
We describe the clinical characteristics of a Chinese family with TSC1 gene mutation and present a literature review of Chinese patients with tuberous sclerosis complex gene mutation reported since 2004. This is the first report of TSC1 R509X mutation in a Chinese family, which might deepen our insight into the clinical and molecular pathogenesis of tuberous sclerosis complex. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - April 22, 2015 Category: Neurology Source Type: research

Erratum to: Genetic Association Between KIBRA Polymorphism and Alzheimer’s Disease with in a Japanese Population
(Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - April 21, 2015 Category: Neurology Source Type: research

Peripheral Vagus Nerve Stimulation Significantly Affects Lipid Composition and Protein Secondary Structure Within Dopamine-Related Brain Regions in Rats
Abstract Recent immunohistochemical studies point to the dorsal motor nucleus of the vagus nerve as the point of departure of initial changes which are related to the gradual pathological developments in the dopaminergic system. In the light of current investigations, it is likely that biochemical changes within the peripheral nervous system may influence the physiology of the dopaminergic system, suggesting a putative role for it in the development of neurodegenerative disorders. By using Fourier transform infrared microspectroscopy, coupled with statistical analysis, we examined the effect of chronic, unilateral...
Source: NeuroMolecular Medicine - April 19, 2015 Category: Neurology Source Type: research

A Dual Inhibitor of Cyclooxygenase and 5-Lipoxygenase Protects Against Kainic Acid-Induced Brain Injury
Abstract Systemic administration of kainic acid causes inflammation and apoptosis in the brain, resulting in neuronal loss. Dual cyclooxygenase/5-lipoxygenase (COX/5-LOX) inhibitors could represent a possible neuroprotective approach in preventing glutamate excitotoxicity. Consequently, we investigated the effects of a dual inhibitor of COX/5-LOX following intraperitoneal administration of kainic acid (KA, 10 mg/kg) in rats. Animals were randomized to receive either the dual inhibitor of COX/5-LOX (flavocoxid, 20 mg/kg i.p.) or its vehicle (1 ml/kg i.p.) 30 min after KA administration. Sham bra...
Source: NeuroMolecular Medicine - April 19, 2015 Category: Neurology Source Type: research

Genetic Association Between KIBRA Polymorphism and Alzheimer’s Disease with in a Japanese Population
Abstract KIBRA plays an important role in synaptic plasticity in human hippocampus related to cognitive function. Functional studies suggest that KIBRA is a potential candidate gene for memory and Alzheimer’s disease (AD) risk. A single nucleotide polymorphism, Rs17070145 C allele affects the onset of AD in an age-dependent manner comparing with T/T genotypes and is also associated with risk of substance abuse and relapse. The aim of this case–control study was to investigate whether the rs17070145 polymorphism affected the onset of AD in an age-dependent manner in a Japanese population. We analysed KI...
Source: NeuroMolecular Medicine - March 24, 2015 Category: Neurology Source Type: research

The Domain II S4-S5 Linker in Nav1.9: A Missense Mutation Enhances Activation, Impairs Fast Inactivation, and Produces Human Painful Neuropathy
In this study, we assayed the mutant channels by voltage-clamp in superior cervical ganglion neurons, which do not produce endogenous Nav1.8 or Nav1.9 currents, and provide a novel platform where Nav1.9 is expressed at relatively high levels. Voltage-clamp analysis showed that the mutation hyperpolarizes (−10.1 mV) channel activation, depolarizes (+6.3 mV) steady-state fast inactivation, slows deactivation, and enhances ramp responses compared with wild-type Nav1.9 channels. Current-clamp analysis showed that the G699R mutant channels render dorsal root ganglion neurons hyperexcitable, via depolarized resti...
Source: NeuroMolecular Medicine - March 20, 2015 Category: Neurology Source Type: research

Circulating MicroRNA Let-7d in Attention-Deficit/Hyperactivity Disorder
Abstract Up to date, there has been no molecular signature available in the clinical practice for attention-deficit/hyperactivity disorder (ADHD). To investigate circulating miRNA let-7d significance in ADHD, we investigated serum miRNA let-7d in 35 newly diagnosed ADHD subjects who were randomly selected from 406 patients out of 7450 children, paired with gender- and age-matched control through case–control study. We observed that circulating miRNA let-7d was significantly higher in ADHD subjects than in control (p 
Source: NeuroMolecular Medicine - February 27, 2015 Category: Neurology Source Type: research

Unfolding the Promise of Translational Targeting in Neurodegenerative Disease
Abstract With the rise of aging populations, new challenges for health care systems are emerging. Degenerative conditions of the central nervous system share a strikingly great deal of similarities, particularly the production and buildup of malfolded proteins. As a result, stress pathways within the endoplasmic reticulum become activated, triggering widespread neuronal apoptosis. New pharmacological compounds targeting this response are emerging as promising treatment strategies. This review examines the current evidence for protein aggregation in neurodegenerative disease states and discusses future mechanisms o...
Source: NeuroMolecular Medicine - February 19, 2015 Category: Neurology Source Type: research

Thymoquinone and Vitamin C Attenuates Pentylenetetrazole-Induced Seizures Via Activation of GABA B1 Receptor in Adult Rats Cortex and Hippocampus
In this study, we investigate the anti-convulsant and neuroprotective effects of thymoquinone (TQ) and vitamin C against pentylenetetrazole (PTZ)-induced generalized seizures. Epileptic seizures were induced in adult rats using systemic intraperitoneal injections of PTZ (50 mg/kg) for 7 days. Animals pretreated with either TQ or vitamin C or in combination attenuated PTZ-induced seizures and mortality in rats as well neurodegeneration in the cells. Compared to PTZ, TQ and vitamin C significantly prolonged the onset of seizures (p > 0.05) as well decrease the high-grade seizures. Analysis of electroen...
Source: NeuroMolecular Medicine - February 14, 2015 Category: Neurology Source Type: research

Sumoylation of p35 Modulates p35/Cyclin-Dependent Kinase (Cdk) 5 Complex Activity
Abstract Cyclin-dependent kinase (Cdk) 5 is critical for central nervous system development and neuron-specific functions including neurite outgrowth as well as synaptic function and plasticity. Cdk5 activity requires association with one of the two regulatory subunits, called p35 and p39. p35 redistribution as well as misregulation of Cdk5 activity is followed by cell death in several models of neurodegeneration. Posttranslational protein modification by small ubiquitin-related modifier (SUMO) proteins (sumoylation) has emerged as key regulator of protein targeting and protein/protein interaction. Under cell-fre...
Source: NeuroMolecular Medicine - February 14, 2015 Category: Neurology Source Type: research

A Candidate Gene Association Study Identifies DAPL1 as a Female-Specific Susceptibility Locus for Age-Related Macular Degeneration (AMD)
Abstract Age-related macular degeneration (AMD) is the leading cause of blindness among white caucasians over the age of 50 years with a prevalence rate expected to increase markedly with an anticipated increase in the life span of the world population. To further expand our knowledge of the genetic architecture of the disease, we pursued a candidate gene approach assessing 25 genes and a total of 109 variants. Of these, synonymous single nucleotide polymorphism (SNP) rs17810398 located in death-associated protein-like 1 (DAPL1) was found to be associated with AMD in a joint analysis of 3,229 cases and 2,...
Source: NeuroMolecular Medicine - February 14, 2015 Category: Neurology Source Type: research

Modification of Hippocampal Markers of Synaptic Plasticity by Memantine in Animal Models of Acute and Repeated Restraint Stress: Implications for Memory and Behavior
Abstract Stress is any condition that impairs the balance of the organism physiologically or psychologically. The response to stress involves several neurohormonal consequences. Glutamate is the primary excitatory neurotransmitter in the central nervous system, and its release is increased by stress that predisposes to excitotoxicity in the brain. Memantine is an uncompetitive N-methyl D-aspartate glutamatergic receptors antagonist and has shown beneficial effect on cognitive function especially in Alzheimer’s disease. The aim of the work was to investigate memantine effect on memory and behavior in animal m...
Source: NeuroMolecular Medicine - February 14, 2015 Category: Neurology Source Type: research

NNZ-2566, a Novel Analog of (1–3) IGF-1, as a Potential Therapeutic Agent for Fragile X Syndrome
Abstract Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. Previous studies have implicated mGlu5 in the pathogenesis of the disease, and many agents that target the underlying pathophysiology of FXS have focused on mGluR5 modulation. In the present work, a novel pharmacological approach for FXS is investigated. NNZ-2566, a synthetic analog of a naturally occurring neurotrophic peptide derived from insulin-like growth factor-1 (IGF-1), was administered to fmr1 knockout mice correcting learning and memory deficits, abnormal hyperactivity and social interaction, normalizing aberr...
Source: NeuroMolecular Medicine - January 23, 2015 Category: Neurology Source Type: research

The Neuroprotective Effect of Salubrinal in a Mouse Model of Traumatic Brain Injury
Abstract We have previously reported that mild traumatic brain injury (mTBI) induced cognitive deficits as well as apoptotic changes in the brains of mice. Apoptosis may be caused by severe, prolonged accumulation of misfolded proteins, and protein aggregation in the endoplasmic reticulum (ER stress). In an additional study, we have reported that mTBI activated the pro-apoptotic arm of the integrated stress response (ISR). The main goal of the present study was to test the involvement of the adaptive eIF2α/ATF4 pathway in mTBI-affected brains. Head injury was induced with a noninvasive, closed-head weight dr...
Source: NeuroMolecular Medicine - January 13, 2015 Category: Neurology Source Type: research

Novel HSAN1 Mutation in Serine Palmitoyltransferase Resides at a Putative Phosphorylation Site That Is Involved in Regulating Substrate Specificity
Abstract 1-Deoxysphingolipids (1-deoxySL) are atypical sphingolipids that are formed by the enzyme serine palmitoyltransferase (SPT) due to a promiscuous use of l-alanine over its canonical substrate l-serine. Several mutations in SPT are associated with the hereditary sensory and autonomic neuropathy type I (HSAN1). The current hypothesis is that these mutations induce a permanent shift in the affinity from l-serine toward l-alanine which results in a pathologically increased 1-deoxySL formation in HSAN1 patients. Also, wild-type SPT forms 1-deoxySL under certain conditions, and elevated levels were found in ...
Source: NeuroMolecular Medicine - January 8, 2015 Category: Neurology Source Type: research

ENT1 Inhibition Attenuates Epileptic Seizure Severity Via Regulation of Glutamatergic Neurotransmission
Abstract Type 1 equilibrative nucleoside transporter (ENT1) promotes glutamate release by inhibition of adenosine signaling. However, whether ENT1 plays a role in epileptic seizure that involves elevated glutamatergic neurotransmission is unknown. Here, we report that both seizure rats and patients show increased expression of ENT1. Intrahippocampal injection of a specific inhibitor of ENT1, nitrobenzylthioinosine (NBTI), attenuates seizure severity and prolongs onset latency. In order to examine whether NBTI would be effective as antiepileptic after peripheral application, we injected NBTI intraperitoneally, and ...
Source: NeuroMolecular Medicine - December 9, 2014 Category: Neurology Source Type: research

The Aβ Peptides-Activated Calcium-Sensing Receptor Stimulates the Production and Secretion of Vascular Endothelial Growth Factor-A by Normoxic Adult Human Cortical Astrocytes
Abstract The excess vascular endothelial growth factor (VEGF) produced in the Alzheimer’s disease (AD) brain can harm neurons, blood vessels, and other components of the neurovascular units (NVUs). But could astrocytes partaking in networks of astrocyte-neuron teams and connected to blood vessels of NVUs contribute to VEGF production? We have shown with cultured cerebral cortical normal (i.e., untransformed) adult human astrocytes (NAHAs) that exogenous amyloid-β peptides (Aβs) stimulate the astrocytes to make and secrete large amounts of Aβs and nitric oxide by a mechanism mediated through t...
Source: NeuroMolecular Medicine - November 10, 2014 Category: Neurology Source Type: research

Dietary Lipid Unsaturation Influences Survival and Oxidative Modifications of an Amyotrophic Lateral Sclerosis Model in a Gender-Specific Manner
Abstract The implication of lipid peroxidation in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) derive from high abundance of peroxidation-prone polyunsaturated fatty acids in central nervous system and its relatively low antioxidant content. In the present work, we evaluated the effect of dietary changes aimed to modify fatty acid tissular composition in survival, disease onset, protein, and DNA oxidative modifications in the hSODG93A transgenic mice, a model of this motor neuron disease. Both survival and clinical evolution is dependent on dietary fatty acid unsaturation and gender, ...
Source: NeuroMolecular Medicine - November 10, 2014 Category: Neurology Source Type: research

Diabetes Mellitus and Disturbances in Brain Connectivity: A Bidirectional Relationship?
Abstract Diabetes mellitus (DM) is associated with deficits across multiple cognitive domains. The observed impairments in cognitive function are hypothesized to be subserved by alterations in brain structure and function. Several lines of evidence indicate that alterations in glial integrity and function, as well as abnormal synchrony within brain circuits and associated networks, are observed in adults with DM. Microangiopathy and alterations in insulin homeostasis appear to be principal effector systems, although a unitary explanation subsuming the complex etiopathology of white matter in DM is unavailable. A ...
Source: NeuroMolecular Medicine - November 10, 2014 Category: Neurology Source Type: research

Lithium/Valproic Acid Combination and l -Glutamate Induce Similar Pattern of Changes in the Expression of miR-30a-5p in SH-SY5Y Neuroblastoma Cells
Abstract It has been proposed that Lithium (Li) and valproic acid (VPA) may be useful to treat neurodegenerative disorders because they protect neurons against excitotoxic insults both in vitro and in vivo models. Moreover, these two drugs may exert their effects by regulating microRNAs (miRNAs), single-stranded and non-coding RNAs able to control gene expression. A subset of the miR-30a family (miR-30a-5p) is involved in the fine-tuning of neuroprotective molecules such as the neurotrophin brain-derived neurotrophic factor (BDNF). Thus, there is the possibility that Li and VPA may alter miR-30a-5p and in turn a...
Source: NeuroMolecular Medicine - November 10, 2014 Category: Neurology Source Type: research

miR26a Modulates T h 17/T reg Balance in the EAE Model of Multiple Sclerosis by Targeting IL6
Abstract A number of different microRNAs (miRNAs) have been implicated in various autoimmune diseases, including multiple sclerosis (MS). T helper (Th)17 and regulatory T cells (Tregs) have likewise been implicated as key players in MS, and a functional imbalance of these cell types is increasingly recognized as a key etiological factor in the disease. Although specific panels of transcription factors and cytokines are known to regulate the Th17/Treg balance, the role of noncoding RNAs remains poorly understood. The inflammatory cytokine, interleukin (IL)6, appears to play a critical role in both the development o...
Source: NeuroMolecular Medicine - November 2, 2014 Category: Neurology Source Type: research

Impairment of Brain Mitochondrial Charybdotoxin- and ATP-Insensitive BK Channel Activities in Diabetes
Abstract Existing evidence indicates an impairment of mitochondrial functions and alterations in potassium channel activities in diabetes. Because mitochondrial potassium channels have been involved in several mitochondrial functions including cytoprotection, apoptosis and calcium homeostasis, a study was carried out to consider whether the gating behavior of the mitochondrial ATP- and ChTx-insensitive Ca2+-activated potassium channel (mitoBKCa) is altered in a streptozotocin (STZ) model of diabetes. Using ion channel incorporation of brain mitochondrial inner membrane into the bilayer lipid membrane, we provi...
Source: NeuroMolecular Medicine - October 25, 2014 Category: Neurology Source Type: research

A Polymorphism in the Promoter Region of the Survivin Gene is Related to Hemorrhagic Transformation in Patients with Acute Ischemic Stroke
Abstract Hemorrhagic transformation (HT) of cerebral infarction is a common and serious occurrence following acute ischemic stroke. The expression of survivin, a member of the inhibitor of apoptosis protein family, has been shown to increase after cerebral ischemia. This protein has been mainly located at the microvasculature within the infarcted and peri-infarcted area, so we aimed to investigate whether survivin gene polymorphisms, also known as BIRC5 gene, were associated with HT of cerebral infarction. Polymorphism screening of the BIRC5 gene was performed in 107 patients with a hemispheric ischemic stroke...
Source: NeuroMolecular Medicine - October 25, 2014 Category: Neurology Source Type: research

Epigenome-Wide Association Study for Parkinson’s Disease
Abstract A methylation-based EWAS on carefully phenotyped individuals with Parkinson’s disease (PD) was conducted to reveal prioritised genes and pathways with statistically significant and sizable changes in PD and in the anxiety that often accompanies it. This was followed by subsequent replication of top-ranked CpG sites. Using the Infinium® HumanMethylation 450K beadchip (Illumina Inc., USA), twenty unique genes with a sizable difference in methylation (P adjusted 
Source: NeuroMolecular Medicine - October 10, 2014 Category: Neurology Source Type: research

Oculopharyngeal Muscular Dystrophy: Phenotypic and Genotypic Studies in a Chinese Population
In this study, we summarized the clinical and genetic characteristics of 34 individuals from 13 unrelated families in Chinese population. In our cohort, the mean age at onset was 47.2 years. Dysphagia, rather than ptosis, was the most common initial symptom. Genetically, we identified seven genotypes in our patients, including one compound heterozygote of (GCN)11/(GCN)12. The genetic heterogeneity implies that there is no single founder effect in Chinese population, and our data also support that the (GCN)11 polymorphism may have a disease-modifying effect. Additionally, the clinical features showed homogeneity within...
Source: NeuroMolecular Medicine - October 5, 2014 Category: Neurology Source Type: research

A Diagnostic Approach for Cerebral Palsy in the Genomic Era
Abstract An ongoing challenge in children presenting with motor delay/impairment early in life is to identify neurogenetic disorders with a clinical phenotype, which can be misdiagnosed as cerebral palsy (CP). To help distinguish patients in these two groups, conventional magnetic resonance imaging of the brain has been of great benefit in “unmasking” many of these genetic etiologies and has provided important clues to differential diagnosis in others. Recent advances in molecular genetics such as chromosomal microarray and next-generation sequencing have further revolutionized the understanding of eti...
Source: NeuroMolecular Medicine - October 4, 2014 Category: Neurology Source Type: research

A Quantitative Assessment of the Association Between 1425G/A Polymorphism in PRKCH and Risk of Stroke
Abstract Previous studies suggested an association between 1425G/A polymorphism in PRKCH and stroke risk, but the results were inconsistent. To obtain a more precise estimation, we carried out a meta-analysis to analyze the effect of 1425G/A SNP in PRKCH on stroke risk. We searched PubMed, ISI Web of Science, Chinese Biomedical Database, China National Knowledge Infrastructure and WANFANG Data for all eligible case–control studies through April 2014. The odds ratios (ORs), together with the 95 % confidence intervals (CIs), were calculated to evaluate the strength of association between 1425G/A SNP and s...
Source: NeuroMolecular Medicine - October 2, 2014 Category: Neurology Source Type: research