Xiao Wenbiao, Yang Zhiquan, Yan Xiaoxin, Feng Li, Long Lili, Tu Tian, Deng Na, Chen Wenjuan, Xiao Bo, Long Hongyu, Zeng Yi
Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
Front Neurol. 2021 Jan 25;11:626013. doi: 10.3389/fneur.2020.626013. eCollection 2020.
Temporal lobe epilepsy (TLE) is the most frequent type of focal epilepsy in adults, typically resistant to pharmacological treatment, and mostly presents with cognitive impairment and psychiatric comorbidities. The most common neuropathological hallmark in TLE patients is hippocampal sclerosis (HS). However, the underlying molecular mechanisms involved remain poorly characterized. The dentate gyrus (DG), one specific hippocampal subarea, structural and functional changes imply a key involvement of the DG in the development of TLE. In this study, a isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic technique was performed for the analysis of hippocampal DG obtained from patients with TLE-HS compared to control samples obtained from autopsy. Our proteomic data identified 5,583 proteins, of which 82 proteins were upregulated and 90 proteins were downregulated. Bioinformatics analysis indicated that differentially expressed proteins were enriched in "synaptic vesicle," "mitochondrion," "cell-cell adhesion," "regulation of synaptic plasticity," "ATP binding," and "oxidative phosphorylation." Protein-protein interaction network analysis found a pivotal module of 10 proteins that were related to "oxidative phosphorylation." This study has investigated proteomic alterations in the DG region of TLE-HS patients, and paved the way for the better understanding of epileptogenesis mechanisms and future therapeutic intervention.
颞叶癫痫（TLE）是成人中最常见的局灶性癫痫类型，通常对药物治疗耐药，且大多伴有认知障碍和精神共病。TLE患者最常见的神经病理学特征是海马硬化（HS）。然而，其潜在的分子机制仍不清楚。齿状回（DG）作为海马的一个特定亚区，其结构和功能变化表明DG在TLE的发生发展中起关键作用。在本研究中，采用基于相对和绝对定量的等压标签（iTRAQ）定量蛋白质组学技术，对TLE-HS患者的海马DG与尸检获得的对照样本进行分析。我们的蛋白质组学数据鉴定出5583种蛋白质，其中82种蛋白质上调，90种蛋白质下调。生物信息学分析表明，差异表达的蛋白质富集于“突触小泡”“线粒体”“细胞间黏附”“突触可塑性调节”“ATP结合”和“氧化磷酸化”。蛋白质-蛋白质相互作用网络分析发现了一个由10种与“氧化磷酸化”相关的蛋白质组成的关键模块。本研究调查了TLE-HS患者DG区域的蛋白质组学改变，为更好地理解癫痫发生机制和未来的治疗干预铺平了道路。
