Vezatin regulates seizures by controlling AMPAR-mediated synaptic activity

作者全名："Wang, You; Yuan, Jinxian; Yu, Xinyuan; Liu, Xi; Tan, Changhong; Chen, Yangmei; Xu, Tao"

作者地址："[Wang, You; Yuan, Jinxian; Liu, Xi; Tan, Changhong; Chen, Yangmei; Xu, Tao] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing 400010, Peoples R China; [Yu, Xinyuan] Chongqing Hosp Tradit Chinese Med, Dept Neurol, Chongqing 400021, Peoples R China"

通信作者："Xu, T (corresponding author), Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing 400010, Peoples R China."

来源：CELL DEATH & DISEASE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000706788800005

JCR分区：Q1

影响因子：9

年份：2021

卷号：12

期号：10

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Although many studies have explored the mechanism of epilepsy, it remains unclear and deserves further investigation. Vezatin has been reported to be a synaptic regulatory protein involved in regulating neuronal synaptic transmission (NST). However, the role of vezatin in epilepsy remains unknown. Therefore, the aims of this study are to investigate the underlying roles of vezatin in epilepsy. In this study, vezatin expression was increased in hippocampal tissues from pilocarpine (PILO)-induced epileptic mice and a Mg2+-free medium-induced in vitro seizure-like model. Vezatin knockdown suppressed seizure activity in PILO-induced epileptic mice. Mechanistically, vezatin knockdown suppressed AMPAR-mediated synaptic events in epileptic mice and downregulated the surface expression of the AMPAR GluA1 subunit (GluA1). Interestingly, vezatin knockdown decreased the phosphorylation of GluA1 at serine 845 and reduced protein kinase A (PKA) phosphorylation; when PKA phosphorylation was suppressed by H-89 (a selective inhibitor of PKA phosphorylation) in vitro, the effects of vezatin knockdown on reducing the phosphorylation of GluA1 at serine 845 and the surface expression of GluA1 were blocked. Finally, we investigated the pattern of vezatin in brain tissues from patients with temporal lobe epilepsy (TLE), and we found that vezatin expression was also increased in patients with TLE. In summary, the vezatin expression pattern is abnormal in individuals with epilepsy, and vezatin regulates seizure activity by affecting AMPAR-mediated NST and the surface expression of GluA1, which is involved in PKA-mediated phosphorylation of GluA1 at serine 845, indicating that vezatin-mediated regulation of epileptic seizures represents a novel target for epilepsy."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81901315, 81901330, 81771390]; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University [kryc-yq-2123]"

基金资助正文："This study was supported by the National Natural Science Foundation of China (Nos. 81901315, 81901330, and 81771390) and supported by the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University (No. kryc-yq-2123), China."