Neuroscience
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The critical period is a time of maximal plasticity within the cortex. The progression of the critical period is marked by experience-dependent transcriptional alterations in cortical neurons, which in turn shifts the excitatory-inhibitory balance in the brain, and accordingly reduces plasticity. Epigenetic mechanisms, such as DNA methylation, control the transcriptional state of neurons, and have been shown to be dynamically regulated during the critical period. ⋯ Pharmacological reduction of DNA methylation in adult animals re-establishes critical period auditory map plasticity. Furthermore, the reduction of DNA methylation in adult animals, reverted intrinsic characteristics of inhibitory synapses to an immature state. Our data suggest that accumulation of DNA methylation during the critical period confers a mature phenotype to cortical neurons, which in turn, facilitates the reduction in plasticity seen after the critical period.
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The basal nucleus of Meynert (BNM) shows structural abnormalities in Parkinson's disease with mild cognitive impairment (PD-MCI). However, it is yet unknown whether functional connectivity (FC) in the BNM (BNM-FC) is altered in patients with PD-MCI. Therefore, in this study, we compared the BNM-FC of patients with PD-MCI and PD patients with normal cognition (PD-NC), to evaluate the relationship between the observed differences of BNM-FC and neuropsychological test scores. ⋯ We found that 86.36% subjects were correctly classified based on the BNM-FC using the leave-one-out cross-validation (LOOCV) method, with a sensitivity of 90.91% and specificity of 81.82%. Our study provides new insights into the neural basis of cognitive dysfunction in PD patients. We also found that BNM-FC can be an effective feature to distinguish PD-MCI from PD-NC.
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The tumor suppressor RNA-binding motif 5 (RBM5) regulates the expression levels and cassette exon-definition (i.e. splicing) of a select set of mRNAs in a tissue-specific manner. Most RBM5-regulated targets were identified in oncological investigations and frequently involve genes which mediate apoptotic cell death. Little is known about the role of RBM5 in the brain. ⋯ Surprisingly, KO increased the mRNA levels of novel targets including casein kinase 2 alpha prime interacting protein (Csnka2ip/CKT2) - a gene not thought to be expressed in the brain, contrary to findings here. Twenty-two unique splicing events were also detected in KOs including increased block-inclusion of cassette exons 20-22 in regulating synaptic membrane exocytosis 2 (Rims2). In conclusion, here we used genome-wide transcriptomic analysis on healthy and injured RBM5 KO mouse brain tissue to elucidate the first known gene targets of this enigmatic RBP in this CNS.
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The exposure-driven olfactory compensation associated with sensory loss is likely to be observed in assessment of food-related dangers. Therefore, in the current study we tested the hypothesis that olfactory compensation occurs in the case of protection from food-related hazards. We compared thresholds for detection of an unpleasant rotten food odor (fermented fish sauce) in four groups of subjects: blind subjects (n = 100), sighted controls (n = 100), deaf subjects (n = 74) and hearing controls (n = 99). ⋯ However, the sensory deprived subjects assessed their sensitivity as higher than did control groups. The present study is yet another example of research among large samples of sensory deprived individuals that shows no evidence of olfactory compensation. This result is consistent with a growing number of studies suggesting no sensory compensation in simple, absolute sensitivity tasks.
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Astrocyte dysfunction, and in particular impaired extracellular potassium spatial buffering, has been postulated to have a potential role in seizure susceptibility and ictogenesis. Inwardly rectifying potassium (Kir) channels, and specifically KIR4.1, have a predominant role in K+ homeostasis and their involvement in neuronal excitability control have been hypothesized. To avoid the severe side effects observed in Kir4.1 cKO, we studied the effects of Kir4.1 down-regulation in cortical astrocytes by using Kir4.1 RNA interference (RNAi) technique combined with in utero electroporation (IUE) at E16 and a piggyBac transposon system. ⋯ Intriguingly, immunohistochemical analysis performed on slices studied with electrophysiology revealed a reduced number of neurons generated from radial glial cells in Kir4.1- rats. We conclude that focal down-regulation of Kir4.1 channel in cortical astrocytes by Kir4.1 RNAi technique combined with IUE is not effective in altering potassium homeostasis and seizure susceptibility. This technique revealed a possible role of Kir4.1 during corticogenesis.