Inhibition of ANXA2 activity attenuates epileptic susceptibility and GluA1 phosphorylation

作者全名："Ma, Limin; Wu, Qingyuan; Yuan, Jinxian; Wang, You; Zhang, Peng; Liu, Qiankun; Tan, Dandan; Liang, Minxue; Chen, Yangmei"

作者地址："[Ma, Limin; Yuan, Jinxian; Wang, You; Zhang, Peng; Liu, Qiankun; Tan, Dandan; Liang, Minxue; Chen, Yangmei] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 2, Chongqing, Peoples R China; [Ma, Limin; Wu, Qingyuan] Chongqing Univ Three Gorges Hosp, Dept Neurol, Chongqing, Peoples R China; [Chen, Yangmei] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 2, Chongqing 400010, Peoples R China"

通信作者："Chen, YM (通讯作者)，Chongqing Med Univ, Dept Neurol, Affiliated Hosp 2, Chongqing 400010, Peoples R China."

来源：CNS NEUROSCIENCE & THERAPEUTICS

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001004626300001

JCR分区：Q1

影响因子：4.8

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：AMPAR; ANXA2; epilepsy; excitatory synaptic transmission; GluA1; seizure

摘要："IntroductionAnnexin A2 (ANXA2) participates in the pathology of a variety of diseases. Nevertheless, the impact of ANXA2 on epilepsy remains to be clarified. AimsHence, the study aimed at investigating the underlying role of ANXA2 in epilepsy through behavioral, electrophysiological, and pathological analyses. ResultsIt was found that ANXA2 was markedly upregulated in the cortical tissues of temporal lobe epilepsy patients (TLE), kainic acid (KA)-induced epilepsy mice, and in a seizure-like model in vitro. ANXA2 silencing in mice suppressed first seizure latency, number of seizures, and seizure duration in behavioral analysis. In addition, abnormal brain discharges were less frequent and shorter in the hippocampal local field potential (LFP) record. Furthermore, the results showed that the frequency of miniature excitatory postsynaptic currents was decreased in ANXA2 knockdown mice, indicating that the excitatory synaptic transmission is reduced. Co-immunoprecipitation (COIP) experiments demonstrated that ANXA2 interacted with the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit GluA1. Moreover, ANXA2 knockdown decreased GluA1 expression on the cell surface and its phosphorylation onserine 831 and serine 845, related to the decreased phosphorylation levels mediated by protein kinases A and C (PKA and PKC). ConclusionsThis study covers a previously unknown and key function of ANXA2 in epilepsy. These findings indicate that ANXA2 can regulate excitatory synaptic activity mediated by AMPAR subunit GluA1 to improve seizure activity, which can provide novel insights for the treatment and prevention of epilepsy."

基金机构："Chongqing Natural Science Foundation, [CSTB2022NSCQ- MSX1203]; National Natural Science Foundation of China [81771390, 82071458]; Chongqing Natural Science Foundation [CSTB2022NSCQ-MSX1203]"

基金资助正文："Chongqing Natural Science Foundation, Grant/Award Number: CSTB2022NSCQ- MSX1203; National Natural Science Foundation of China, Grant/Award Number: 81771390 and 82071458This work was supported by the National Natural Science Foundation of China, Grant/Award Number: 82071458 and 81771390. This research was also supported by Chongqing Natural Science Foundation, Grant/Award Number: CSTB2022NSCQ-MSX1203."