Sorbs2 regulates seizure activity by influencing AMPAR-mediated excitatory synaptic transmission in temporal lobe epilepsy

作者全名：Ban, Yuenan; Yang, Xiaolan; Tan, Dandan; Gong, Chen; Gao, Yuan; Yuan, Jinxian; Chen, Yangmei; Wang, You; Xu, Tao

作者地址：[Ban, Yuenan; Yang, Xiaolan; Tan, Dandan; Gong, Chen; Gao, Yuan; Yuan, Jinxian; Chen, Yangmei; Wang, You; Xu, Tao] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurol, Chongqing 400010, Peoples R China

通信作者：Wang, Y; Xu, T (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Neurol, Chongqing 400010, Peoples R China.

来源：NEUROCHEMISTRY INTERNATIONAL

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001223659800001

JCR分区：Q1

影响因子：4.4

年份：2024

卷号：176

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Epilepsy; Temporal lobe epilepsy; Sorbs2; AMPAR; Excitatory synaptic transmissions

摘要：Temporal lobe epilepsy (TLE), the most common type of drug-resistant epilepsy, severely affects quality of life. However, the underlying mechanism of TLE remains unclear and deserves further exploration. Sorbs2, a key synaptic regulatory protein, plays an important role in the regulation of synaptic transmission in the mammalian brain. In this study, we aimed to investigate the expression pattern of Sorbs2 in a kainic acid (KA)-induced TLE mouse model and in patients with TLE to further determine whether Sorbs2 is involved in seizure activity and to explore the potential mechanism by which Sorbs2 affects seizures in this TLE mouse model. First, we found that the expression of Sorbs2 was obviously increased in the hippocampus and cortex of a TLE mouse model and in the temporal cortex of TLE patients, indicating an abnormal expression pattern of Sorbs2 in TLE. Importantly, subsequent behavioral analyses and local field potential (LFP) analyses of a TLE mouse model demonstrated that the downregulation of hippocampal Sorbs2 could prolong the latency to spontaneous recurrent seizures (SRSs) and protect against SRSs. We also found that the knockdown of Sorbs2 in the hippocampus could decrease excitatory synaptic transmission in pyramidal neurons (PNs) in the hippocampal CA1 region and reduce the expression levels of the AMPAR subunits GluA1 and GluA2. Thus, we speculated that Sorbs2 may promote epileptogenesis and the development of TLE by affecting AMPAR-mediated excitatory synaptic transmission in PNs in the CA1 region. Therefore, reducing the expression of hippocampal Sorbs2 could restrain epileptogenesis and the development of TLE.

基金机构：Chongqing Natural Science Foundation [CSTB2022NSCQ-MSX0117, CSTB2023NSCQ-MSX0101]; Science and Technology Research Program of Chongqing Education Commission of China [KJQN202300402]; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University of China [kryc-yq-2123]

基金资助正文：This study was supported by the Chongqing Natural Science Foundation (No. CSTB2022NSCQ-MSX0117, CSTB2023NSCQ-MSX0101) , the Science and Technology Research Program of Chongqing Education Commission of China (KJQN202300402) , and the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University of China (No. kryc-yq-2123) .