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

Spinal Cord Injury and the Neuron-Intrinsic Regeneration-Associated Gene Program
Abstract Spinal cord injury (SCI) affects millions of people worldwide and causes a significant physical, emotional, social and economic burden. The main clinical hallmark of SCI is the permanent loss of motor, sensory and autonomic function below the level of injury. In general, neurons of the central nervous system (CNS) are incapable of regeneration, whereas injury to the peripheral nervous system is followed by axonal regeneration and usually results in some degree of functional recovery. The weak neuron-intrinsic regeneration-associated gene (RAG) response upon injury is an important reason for the failure of...
Source: NeuroMolecular Medicine - October 1, 2014 Category: Neurology Source Type: research

Multiple Mechanisms of Iron-Induced Amyloid Beta-Peptide Accumulation in SHSY5Y Cells: Protective Action of Negletein
In this study, we have shown that exogenously added iron in the form of ferric ammonium citrate (FAC) leads to considerable accumulation of amyloid precursor protein (APP) without a corresponding change in the concerned gene expression in cultured SHSY5Y cells during exposure up to 48 h. This phenomenon is also associated with increased β-secretase activity and augmented release of amyloid beta 42 in the medium. Further, the increase in β-secretase activity, in SHSY5Y cells, upon exposure to iron apparently involves reactive oxygen species (ROS) and NF-κB activation. The synthetic flavone negletei...
Source: NeuroMolecular Medicine - September 24, 2014 Category: Neurology Source Type: research

MicroRNA Expression Signatures and Their Correlation with Clinicopathological Features in Glioblastoma Multiforme
Abstract The increasing interest in identifying molecular biomarkers to determine patient prognosis in glioblastoma multiforme (GBM) has resulted in several microRNA (miRNA)-based signatures able to predict progression-free and overall survival. However, the coherency between these signatures is small, and correlations to clinicopathological features other than survival are seldom seen. The aim of this study was to identify any significant relationship between miRNA signatures and clinicopathological data by combining pathological features with miRNA and mRNA analysis in fourteen GBM patients. In total, 161 miRNA...
Source: NeuroMolecular Medicine - September 1, 2014 Category: Neurology Source Type: research

Methylation and Expression Patterns of Tropomyosin-Related Kinase Genes in Different Grades of Glioma
Abstract Tropomyosin-related kinase family (NTRK1, NTRK2 and NTRK3) is well known to play an important role in the pathogenesis of brain tumour, which exhibit heterogeneity in its biological and clinical behaviour. However, the mechanism that regulates NTRKs in glioma is not well understood. The present study investigates the epigenetic status (methylation) of NTRKs and their expression in different grades of glioma. Promoter methylation and structural relationship of NTRKs was assessed using methylation-specific PCR followed by chromatin immunoprecipitation in brain tissue samples from 220 subjects with diff...
Source: NeuroMolecular Medicine - September 1, 2014 Category: Neurology Source Type: research

MicroRNA Expression Profile and Functional Analysis Reveal that miR-206 is a Critical Novel Gene for the Expression of BDNF Induced by Ketamine
Abstract Depression is a major social and health concern, and ketamine exerts a quick, remarkable and persistent anti-depressive effect. microRNAs (miRNAs) show remarkable potential in the treatment of clinical depression. Here, we determined the expression profile of miRNAs in the hippocampus of rats treated with ketamine (15 mg/kg). The results suggest that multiple miRNAs were aberrantly expressed in rat hippocampus after ketamine injection (18 miRNAs were significantly reduced, while 22 miRNAs were significantly increased). Among them, miR-206 was down-regulated in ketamine-treated rats. In both cultured...
Source: NeuroMolecular Medicine - September 1, 2014 Category: Neurology Source Type: research

Functions of the CB1 and CB2 Receptors in Neuroprotection at the Level of the Blood–Brain Barrier
Abstract The cannabinoid (CB) receptors are the main targets of the cannabinoids, which include plant cannabinoids, endocannabinoids and synthetic cannabinoids. Over the last few years, accumulated evidence has suggested a role of the CB receptors in neuroprotection. The blood–brain barrier (BBB) is an important brain structure that is essential for neuroprotection. A link between the CB receptors and the BBB is thus likely, but this possible connection has only recently gained attention. Cannabinoids and the BBB share the same mechanisms of neuroprotection and both protect against excitotoxicity (CB1), cel...
Source: NeuroMolecular Medicine - September 1, 2014 Category: Neurology Source Type: research

In-Depth Characterisation of Retinal Pigment Epithelium (RPE) Cells Derived from Human Induced Pluripotent Stem Cells (hiPSC)
Abstract Induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) has widely been appreciated as a promising tool to model human ocular disease emanating from primary RPE pathology. Here, we describe the successful reprogramming of adult human dermal fibroblasts to iPSCs and their differentiation to pure expandable RPE cells with structural and functional features characteristic for native RPE. Fibroblast cultures were established from skin biopsy material and subsequently reprogrammed following polycistronic lentiviral transduction with OCT4, SOX2, KLF4 and L-Myc. Fibroblast-derived iPSCs sh...
Source: NeuroMolecular Medicine - September 1, 2014 Category: Neurology Source Type: research

Endothelial Activation and Chemoattractant Expression are Early Processes in Isolated Blast Brain Injury
This study shows that blast brain injury is no exception, and the data provide important mechanistic clues regarding the drivers of such inflammation. Whilst this effect alone is unlikely to be responsible for the totality of consequences of blast brain injury, it suggests a mechanism that may be priming the cerebral inflammatory response and rendering cerebral tissue more susceptible to the deleterious effects of systemic inflammatory reactions. (Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - September 1, 2014 Category: Neurology Source Type: research

Mutation Analysis of MFN2, GJB1, MPZ and PMP22 in Italian Patients with Axonal Charcot–Marie–Tooth Disease
Abstract Charcot–Marie–Tooth (CMT) diseases include a group of clinically heterogeneous inherited neuropathies subdivided into demyelinating (CMT1), axonal (CMT2) and intermediate CMT forms. CMTs are associated with different genes, although mutations in some of these genes may cause both clinical pictures. To date, more than 50 CMT genes have been identified, but more than half of the cases are due to mutations in MFN2, MPZ, GJB1 and PMP22. The aim of this study was to estimate the frequency of disease mutations of these four genes in the axonal form of CMT in order to evaluate their effectivene...
Source: NeuroMolecular Medicine - September 1, 2014 Category: Neurology Source Type: research

HIF-1α Genetic Variants and Protein Expression Confer the Susceptibility and Prognosis of Gliomas
Abstract To investigate the role of HIF-1α genetic polymorphism of c.1772C>T and c.1790G>A in the incidence and prognosis of gliomas in a Chinese cohort, a total of 387 gliomas patients and 437 age- and sex-matched healthy controls were recruited. The genetic polymorphism of c.1772C>T and c.1790G>A was determined. We found that the genotype distribution at c.1772C>T showed significant difference between patients and controls. Multivariable analyses showed a significantly higher risk for gliomas in 1772TT genotype carriers (odds ratio 2.68, with CC as reference). In addition, we also found a s...
Source: NeuroMolecular Medicine - September 1, 2014 Category: Neurology Source Type: research

Association of Endothelial Nitric Oxide Synthase Gene Polymorphisms (894G/T, −786T/C, G10T) and Clinical Findings in Patients with Migraine
Abstract Migraine is a common neurological disorder characterized by recurrent attacks, unilateral head pain, and related symptoms. The aim of this study was to investigate three endothelial nitric oxide synthase (eNOS) polymorphisms in 176 patients with migraine and 123 healthy individuals. Clinical and biochemical parameters were investigated. Genetic analysis was performed using the polymerase chain reaction–restriction fragment length polymorphism method. The differences between migraine cases and the control group were significant for two polymorphisms (−786T/C and 894G/T) (p = 0.00...
Source: NeuroMolecular Medicine - September 1, 2014 Category: Neurology Source Type: research

Erratum to: Genomic Binding Sites and Biological Effects of the Vitamin D–VDR Complex in Multiple Sclerosis
(Source: NeuroMolecular Medicine)
Source: NeuroMolecular Medicine - September 1, 2014 Category: Neurology Source Type: research

Propofol Protects Against Angiotensin II-Induced Mouse Hippocampal HT22 Cells Apoptosis Via Inhibition of p66Shc Mitochondrial Translocation
In this study, we investigated the mechanism how propofol protected mouse hippocampal HT22 cells against angiotensin II-induced oxidative stress and apoptosis. Cell viability was evaluated with CCK8 kit. Protein expressions of active caspase 3, cytochrome c, p66Shc, p-p66shc–Ser36, protein kinase C βII (PKCβII), Pin-1 and phosphatase A2 (PP2A) were measured by Western blot. Superoxide anion (O 2 .− ) accumulation was measured with the reduction of ferricytochrome c. Compared with the control group, angiotensin II up-regulated expression of PKCβII, Pin-1 and PP2A, i...
Source: NeuroMolecular Medicine - August 24, 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 af...
Source: NeuroMolecular Medicine - August 23, 2014 Category: Neurology Source Type: research

No Association Between NRG1 and ErbB4 Genes and Psychopathological Symptoms of Schizophrenia
Abstract Neuregulin 1 (NRG1) and v-erb-a erythroblastic leukemia viral oncogene homolog 4 (ErbB4) have been extensively studied in schizophrenia susceptibility because of their pivotal role in key neurodevelopmental processes. One of the reasons for the inconsistencies in results could be the fact that the phenotype investigated has mostly the diagnosis of schizophrenia per se, which is widely heterogeneous, both clinically and biologically. In the present study we tested, in a large cohort of 461 schizophrenia patients recruited in Scotland, whether several SNPs in NRG1 and/or ErbB4 are associated with schizo...
Source: NeuroMolecular Medicine - August 21, 2014 Category: Neurology Source Type: research

Direct Effect of Bevacizumab on Glioblastoma Cell Lines In Vitro
In this report, we studied whether bevacizumab can act directly on malignant glioblastoma cells. We observe changes in the expression profiles of components of the VEGF/VEGF-R pathway and in the response to a VEGF-A stimulus following bevacizumab treatment. In addition, we show that bevacizumab itself acts on glioblastoma cells by activating the Akt and Erks survival signaling pathways. Bevacizumab also enhances proliferation and invasiveness of glioblastoma cells in hyaluronic acid hydrogel. We propose that the paradoxical effect of bevacizumab on glioblastoma cells could be due to changes in the VEGF-A-dependent autocrin...
Source: NeuroMolecular Medicine - August 13, 2014 Category: Neurology Source Type: research

Mitochondrial Oxidative Phosphorylation Transcriptome Alterations in Human Amyotrophic Lateral Sclerosis Spinal Cord and Blood
Abstract Origins of onset and progression of motor neurodegeneration in amyotrophic lateral sclerosis (ALS) are not clearly known, but may include impairment of mitochondrial bioenergetics. We used quantitative PCR approaches to analyze the mitochondrial oxidative phosphorylation (OXPHOS) transcriptomes of spinal cord tissue and peripheral blood mononuclear cells (PBMC) from persons with sporadic ALS compared with those without neurological disease. Expression measurements of 88 different nuclear (n) and mitochondrial (mt) DNA-encoded OXPHOS genes showed mtDNA-encoded respiratory gene expression was significantly ...
Source: NeuroMolecular Medicine - August 1, 2014 Category: Neurology Source Type: research

Inhibitors of Histone Deacetylases Enhance Neurotoxicity of DNA Damage
Abstract The nonselective inhibitors of class I/II histone deacetylases (HDACs) including trichostatin A and the clinically used suberoylanilide hydroxamic acid (SAHA, vorinostat) are neuroprotective in several models of neuronal injury. Here, we report that in cultured cortical neurons from newborn rats and in the cerebral cortex of whole neonate rats, these HDAC inhibitors exacerbated cytotoxicity of the DNA double-strand break (DSB)-inducing anticancer drug etoposide by enhancing apoptosis. Similar neurotoxic interactions were also observed in neurons that were treated with other DNA damaging drugs including ci...
Source: NeuroMolecular Medicine - July 26, 2014 Category: Neurology Source Type: research

Aberrant DNA Methylation of Blood in Schizophrenia by Adjusting for Estimated Cellular Proportions
In this study, we performed a genome-wide DNA methylation profiling of the peripheral leukocytes from patients with SCZ and from non-psychiatric controls (N = 105; 63 SCZ and 42 control subjects) using a quantitative high-resolution DNA methylation microarray which covered across the whole gene region (485,764 CpG dinucleotides). In the DNA methylation data analysis, we first estimated the cell-type proportions of each sample with a published algorithm. Next, we performed a surrogate variable analysis to identify potential confounding factors in our microarray data. Finally, we conducted a multiple linear regress...
Source: NeuroMolecular Medicine - July 23, 2014 Category: Neurology Source Type: research

Phosphoinositide 3-Kinase γ Affects LPS-Induced Disturbance of Blood–Brain Barrier Via Lipid Kinase-Independent Control of cAMP in Microglial Cells
Abstract The breakdown of the blood–brain barrier (BBB) is a key event in the development of sepsis-induced brain damage. BBB opening allows blood-born immune cells to enter the CNS to provoke a neuroinflammatory response. Abnormal expression and activation of matrix metalloproteinases (MMP) was shown to contribute to BBB opening. Using different mouse genotypes in a model of LPS-induced systemic inflammation, our present report reveals phosphoinositide 3-kinase γ (PI3Kγ) as a mediator of BBB deterioration and concomitant generation of MMP by microglia. Unexpectedly, microglia expressing lipid ki...
Source: NeuroMolecular Medicine - July 18, 2014 Category: Neurology Source Type: research

Apolipoprotein E Isoform-Specific Effects on Lipoprotein Receptor Processing
Abstract Recent findings indicate an isoform-specific role for apolipoprotein E (apoE) in the elimination of beta-amyloid (Aβ) from the brain. ApoE is closely associated with various lipoprotein receptors, which contribute to Aβ brain removal via metabolic clearance or transit across the blood–brain barrier (BBB). These receptors are subject to ectodomain shedding at the cell surface, which alters endocytic transport and mitigates Aβ elimination. To further understand the manner in which apoE influences Aβ brain clearance, these studies investigated the effect of apoE on lipoprotein recep...
Source: NeuroMolecular Medicine - July 12, 2014 Category: Neurology Source Type: research