Department of Pediatrics, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, 05403-900, Brazil.
Department of Neurology, Faculdade de Ciências Médicas da Universidade Estadual de Campinas, UNICAMP, Campinas, SP, 13083-887, Brazil.
Sci Rep. 2021 May 13;11(1):10257. doi: 10.1038/s41598-021-89802-3.
In about a third of the patients with epilepsy the seizures are not drug-controlled. The current limitation of the antiepileptic drug therapy derives from an insufficient understanding of epilepsy pathophysiology. In order to overcome this situation, it is necessary to consider epilepsy as a disturbed network of interactions, instead of just looking for changes in single molecular components. Here, we studied CA3 transcriptional signatures and dentate gyrus histopathologic alterations in hippocampal explants surgically obtained from 57 RMTLE patients submitted to corticoamygdalohippocampectomy. By adopting a systems biology approach, integrating clinical, histopathological, and transcriptomic data (weighted gene co-expression network analysis), we were able to identify transcriptional modules highly correlated with age of disease onset, cognitive dysfunctions, and granule cell alterations. The enrichment analysis of transcriptional modules and the functional characterization of the highly connected genes in each trait-correlated module allowed us to unveil the modules' main biological functions, paving the way for further investigations on their roles in RMTLE pathophysiology. Moreover, we found 15 genes with high gene significance values which have the potential to become novel biomarkers and/or therapeutic targets in RMTLE.
大约三分之一的癫痫患者的癫痫发作无法通过药物控制。抗癫痫药物治疗的当前局限性源于对癫痫病理生理学的理解不足。为了克服这种情况，有必要将癫痫视为受干扰的相互作用网络，而不仅仅是寻找单个分子成分的变化。在这里，我们研究了从 57 名接受皮质杏仁核海马切除术的 RMTLE 患者手术获得的海马离体中的 CA3 转录特征和齿状回组织病理学改变。通过采用系统生物学方法，整合临床、组织病理学和转录组数据（加权基因共表达网络分析），我们能够识别与疾病发病年龄、认知功能障碍和颗粒细胞改变高度相关的转录模块。转录模块的富集分析和每个与特征相关模块中高度连接基因的功能特征使我们能够揭示模块的主要生物学功能，为进一步研究它们在 RMTLE 病理生理学中的作用铺平了道路。此外，我们发现了 15 个具有高基因意义值的基因，它们有可能成为 RMTLE 的新生物标志物和/或治疗靶点。
