Modulation Of Neuronal Signaling Research Articles

Sex differences in the neuroendocrine control of metabolism and the implication of astrocytes.

Males and females have distinct propensities to develop obesity and its related comorbidities, partially due to gonadal steroids. There are sex differences in hypothalamic neuronal circuits, as well as in astrocytes, that participate in metabolic control and the development of obesity-associated complications. Astrocytes are involved in nutrient transport and metabolism, glucose sensing, synaptic remodeling and modulation of neuronal signaling. They express receptors for metabolic hormones and mediate effects of these metabolic signals on neurons, with astrogliosis occurring in response to high fat diet and excess weight gain. However, most studies of obesity have focused on males. Recent reports indicate that male and female astrocytes respond differently to metabolic signals and this could be involved in the differential response to high fat diet and the onset of obesity-associated pathologies. Here we focus on the sex differences in response to obesogenic paradigms and the possible role of hypothalamic astrocytes in this phenomenon.

Association between Common Single- nucleotide Polymorphism of Reelin Gene, rs736707 (C/T) with Autism Spectrum Disorder in Iranian-Azeri Patients

Introduction Reelin gene (RELN) codes a large extracellular matrix glycoprotein with serine protease activity and is implicated in the modulation of neuronal signaling, synaptic transmission and plasticity. The reelin plays a fundamental and pivotal role in the development of laminar structures and may be one of the loci contributing to the positive linkage between chromosome 7q and autistic disorder. This study was performed to examine the association of a frequent genetic variation in reelin gene, rs736707 (C/T), with Autism risk among Iranian-Azeri population. Materials and Methods A case–control association study included 74 patients with Autism spectrum disorder (ASD) and 86 healthy subjects. Genomic DNA was extracted from peripheral blood samples by salting-out method. Single nucleotide polymorphisms (SNP) genotyping was carried out by Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) technique. The collected data were analyzed through java stant online statistics software, using Chi-square, with a significance level of 0.05. Results Significant differences in the allele and genotype frequencies between cases and controls were not observed (P>0.05). The rs736707SNP was not associated with Autism predisposition in Iranian-Azeri children. Conclusion Based on our results, the rs736707 SNP could not be used as a useful molecular biomarker to predict genetic susceptibility for autism spectrum disorder in Iranian-Azeri patients.

Excitotoxic protection by polyanionic polysaccharide: Evidence of a cell survival pathway involving AMPA receptor–MAPK Interactions

Growing numbers of studies indicate that polysaccharides influence signaling events important for brain function. It has been speculated that such polysaccharide modulation of neuronal signals can promote synaptogenesis and cell maintenance. Here, we tested whether dextran sulfate, a polyanion that mimics natural mucopolysaccharides, protects hippocampal neurons against excitotoxic insults. An excitotoxin was applied to primary hippocampal cultures in the absence or presence of a large 500-kDa dextran sulfate (DS-L), a smaller 5-8-kDa species (DS-S), or sulfate-free dextran of 500 kDa. Only DS-L prevented neuronal damage as determined by a membrane permeability assay and phase contrast morphology. The sulfate and size dependence is also characteristic of DS-L's modulatory action on the channel activity of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors. The extent of neuroprotection correlates with the level of modulation of AMPA responses, and DS-L exhibits comparable EC(50) values for the two effects (3-7 nM). DS-L also modulates the link between AMPA receptors and mitogen-activated protein kinase (MAPK) involving extracellular signal-regulated protein kinase (ERK), well known for its involvement in cell survival and repair. Correspondingly, protection against N-methyl-D-aspartate (NMDA) excitotoxicity was evident in hippocampal slice cultures when DS-L was applied 30 min postinsult. These findings suggest that polysaccharides elicit neuroprotection in the brain, including enhanced repair responses through the AMPA receptor-MAPK axis.