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Multi‐omics analysis suggests enhanced epileptogenesis in the Cornu Ammonis 3 of the pilocarpine model of mesial temporal lobe epilepsy
Hippocampus ( IF 2.4 ) Pub Date : 2020-10-10 , DOI: 10.1002/hipo.23268
Amanda M Canto 1, 2 , Alexandre H B Matos 1, 2 , Alexandre B Godoi 1, 2 , André S Vieira 2, 3 , Beatriz B Aoyama 2, 3 , Cristiane S Rocha 1, 2 , Barbara Henning 1, 2 , Benilton S Carvalho 2, 4 , Vinicius D B Pascoal 5 , Diogo F T Veiga 6 , Rovilson Gilioli 7 , Fernando Cendes 2, 8 , Iscia Lopes-Cendes 1, 2
Affiliation  

Mesial temporal lobe epilepsy (MTLE) is a chronic neurological disorder characterized by the occurrence of seizures, and histopathological abnormalities in the mesial temporal lobe structures, mainly hippocampal sclerosis (HS). We used a multi‐omics approach to determine the profile of transcript and protein expression in the dorsal and ventral hippocampal dentate gyrus (DG) and Cornu Ammonis 3 (CA3) in an animal model of MTLE induced by pilocarpine. We performed label‐free proteomics and RNAseq from laser‐microdissected tissue isolated from pilocarpine‐induced Wistar rats. We divided the DG and CA3 into dorsal and ventral areas and analyzed them separately. We performed a data integration analysis and evaluated enriched signaling pathways, as well as the integrated networks generated based on the gene ontology processes. Our results indicate differences in the transcriptomic and proteomic profiles among the DG and the CA3 subfields of the hippocampus. Moreover, our data suggest that epileptogenesis is enhanced in the CA3 region when compared to the DG, with most abnormalities in transcript and protein levels occurring in the CA3. Furthermore, our results show that the epileptogenesis in the pilocarpine model involves predominantly abnormal regulation of excitatory neuronal mechanisms mediated by N‐methyl D‐aspartate (NMDA) receptors, changes in the serotonin signaling, and neuronal activity controlled by calcium/calmodulin‐dependent protein kinase (CaMK) regulation and leucine‐rich repeat kinase 2 (LRRK2)/WNT signaling pathways.

中文翻译:

多组学分析表明,在颞叶内侧癫痫的毛果芸香碱模型的 Cornu Ammonis 3 中增强了癫痫发生

颞叶内侧癫痫 (MTLE) 是一种慢性神经系统疾病,其特征是发生癫痫发作和颞叶内侧结构的组织病理学异常,主要是海马硬化 (HS)。我们使用多组学方法来确定背侧和腹侧海马齿状回 (DG) 和Cornu Ammonis的转录和蛋白质表达谱3 (CA3) 在毛果芸香碱诱导的 MTLE 动物模型中。我们对从毛果芸香碱诱导的 Wistar 大鼠中分离的激光显微切割组织进行了无标记蛋白质组学和 RNAseq。我们将 DG 和 CA3 分为背侧和腹侧区域并分别进行分析。我们进行了数据集成分析并评估了丰富的信号通路,以及基于基因本体过程生成的集成网络。我们的结果表明海马 DG 和 CA3 亚区之间的转录组和蛋白质组谱存在差异。此外,我们的数据表明,与 DG 相比,CA3 区域的癫痫发生增强,大多数转录物和蛋白质水平异常发生在 CA3。此外,
更新日期:2020-10-10
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