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RNA测序揭示了经典海马硬化模型中与癫痫发生相关的区域特异性分子机制。

RNA sequencing reveals region-specific molecular mechanisms associated with epileptogenesis in a model of classical hippocampal sclerosis.

作者信息

Vieira A S, de Matos A H, do Canto A M, Rocha C S, Carvalho B S, Pascoal V D B, Norwood B, Bauer S, Rosenow F, Gilioli R, Cendes F, Lopes-Cendes I

机构信息

Department of Medical Genetics, School of Medical Sciences, University of Campinas - UNICAMP, SP, BRAZIL.

Faculty of Basic Sciences, Fluminense Federal University, Nova Friburgo, Rio de Janeiro, Brazil UFF.

出版信息

Sci Rep. 2016 Mar 3;6:22416. doi: 10.1038/srep22416.

Abstract

We report here the first complete transcriptome analysis of the dorsal (dDG) and ventral dentate gyrus (vDG) of a rat epilepsy model presenting a hippocampal lesion with a strict resemblance to classical hippocampal sclerosis (HS). We collected the dDG and vDG by laser microdissection 15 days after electrical stimulation and performed high-throughput RNA-sequencing. There were many differentially regulated genes, some of which were specific to either of the two sub-regions in stimulated animals. Gene ontology analysis indicated an enrichment of inflammation-related processes in both sub-regions and of axonal guidance and calcium signaling processes exclusively in the vDG. There was also a differential regulation of genes encoding molecules involved in synaptic function, neural electrical activity and neuropeptides in stimulated rats. The data presented here suggests, in the time point analyzed, a remarkable interaction among several molecular components which takes place in the damaged hippocampi. Furthermore, even though similar mechanisms may function in different regions of the DG, the molecular components involved seem to be region specific.

摘要

我们在此报告了对一种大鼠癫痫模型的背侧齿状回(dDG)和腹侧齿状回(vDG)的首次完整转录组分析,该模型呈现出海马损伤,与经典海马硬化(HS)极为相似。在电刺激15天后,我们通过激光显微切割收集了dDG和vDG,并进行了高通量RNA测序。存在许多差异调节基因,其中一些在受刺激动物的两个亚区域中是各自特有的。基因本体分析表明,两个亚区域均富集了与炎症相关的过程,而轴突导向和钙信号传导过程仅在vDG中富集。在受刺激的大鼠中,参与突触功能、神经电活动和神经肽的分子编码基因也存在差异调节。此处呈现的数据表明,在所分析的时间点,受损海马中发生了几种分子成分之间的显著相互作用。此外,尽管类似的机制可能在齿状回的不同区域起作用,但所涉及的分子成分似乎具有区域特异性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42df/4776103/dab6e2a900ca/srep22416-f1.jpg

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