Syntabulin regulates neuronal excitation/inhibition balance and epileptic seizures by transporting syntaxin 1B

作者全名："Ke, Pingyang; Gu, Juan; Liu, Jing; Liu, Yan; Tian, Xin; Ma, Yuanlin; Meng, Yuan; Xiao, Fei"

作者地址："[Ke, Pingyang; Gu, Juan; Liu, Jing; Liu, Yan; Tian, Xin; Ma, Yuanlin; Meng, Yuan; Xiao, Fei] Chongqing Med Univ, Dept Neurol, Chongqing Key Lab Neurol, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Gu, Juan] Southwest Med Univ, Affiliated Tradit Chinese Med Hosp, Dept Neurol, Luzhou 646000, Peoples R China"

通信作者："Xiao, F (通讯作者)，Chongqing Med Univ, Dept Neurol, Chongqing Key Lab Neurol, Affiliated Hosp 1, Chongqing 400016, Peoples R China."

来源：CELL DEATH DISCOVERY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001018447600002

JCR分区：Q1

影响因子：6.1

年份：2023

卷号：9

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Epilepsy is a widespread neurological disorder affecting more than 65 million people, but the mechanisms of epilepsy remains unknown. Abnormal synaptic transmission has a crucial role in the occurrence and development of epilepsy. Here, we found that syntabulin, a neuronal transporter, was mainly localized in neurons, and its expression was increased in epileptic tissues. Knockdown of syntabulin increased susceptibility and severity of epilepsy, whereas overexpression of syntabulin had the opposite effect. Mechanistically, in the epileptic brain tissue, syntabulin mainly translocated syntaxin 1B (STX1B) rather than syntaxin 1A (STX1A) to the presynaptic membrane, which resulted in increased presynaptic transmitter release. Further studies showed that syntabulin had a more significant effect on presynaptic functionality of GABAergic activity over that of excitatory synapses and resulted in an excitation/inhibition (E/I) imbalance, thereby regulating the epileptic phenotype. In addition, we found that the increased expression of syntabulin in epileptic brain tissue was mainly regulated by transcription factor TFAP2A. In summary, syntabulin plays a protective role in epilepsy by maintaining a proper E/I balance in the hippocampus."

基金机构："National Natural Science Foundation of China [81873788, 81922023, 82271496, 82001378]; Future Medical Youth Innovation Team Program of Chongqing Medical University [W0043]; National Natural Science Foundation of Chongqing [CSTB2022NSCQ-MSX0747, cstc2021ycjh-bgzxm0035]; Young and Middle-aged Medical Excellence Team Program of Chongqing; Chongqing Chief Expert Studio program; Science and Technology Research Program of Chongqing Education Commission [KJQN202200435]; Chongqing Talents: Exceptional Young Talents Project [CQYC202005014]"

基金资助正文："<STRONG>& nbsp;</STRONG>This study was supported by National Natural Science Foundation of China (No. 81873788, 81922023, 82271496, 82001378), Future Medical Youth Innovation Team Program of Chongqing Medical University (No. W0043), National Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0747, cstc2021ycjh-bgzxm0035), Young and Middle-aged Medical Excellence Team Program of Chongqing, Chongqing Chief Expert Studio program, Science and Technology Research Program of Chongqing Education Commission (KJQN202200435), Chongqing Talents: Exceptional Young Talents Project (CQYC202005014)."