Decreased Spire2 Expression is Involved in Epilepsy

作者全名："Hao, Lixia; Zhang, Hui; Peng, Xiaoyan; Yang, Yi; Yang, Min; Guo, Yi; Wang, Xuefeng; Jing, Wei"

作者地址："[Hao, Lixia; Zhang, Hui; Peng, Xiaoyan; Yang, Yi; Yang, Min; Guo, Yi; Wang, Xuefeng; Jing, Wei] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing Key Lab Neurol, Chongqing, Peoples R China; [Hao, Lixia] Inner Mongolia Med Univ, Affiliated Hosp, Dept Rehabil Med, Hohhot, Peoples R China; [Jing, Wei] Shanxi Med Univ, Hosp 3, Tongji Shanxi Hosp, Shanxi Bethune Hosp,Shanxi Acad Med Sci,Dept Neuro, Taiyuan, Shanxi, Peoples R China; [Jing, Wei] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China"

通信作者："Wang, XF; Jing, W (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing Key Lab Neurol, Chongqing, Peoples R China."

来源：NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000872588400001

JCR分区：Q3

影响因子：3.3

年份：2022

卷号：504

期号：　

开始页：1

结束页：9

文献类型：Article

关键词：Temporal lobe epilepsy (TLE); Spire2; neuronal excitability; epileptogenesis

摘要："Epilepsy is a neurological disorder caused by abnormally elevated neuronal firing and excitability. Spire2, also known as the nucleating factor of F-actin, plays an important role in long-range vesicle transport. This study showed that Spire2 was highly expressed in neurons in the cortex and hippocampus. Its knockdown significantly reduced the initiation current of the evoked action potential and the frequency of action potential, suggesting that Spire2 knockdown inhibits the threshold current of the neuron. In the cortex of patients with refractory temporal lobe epilepsy (TLE), Spire2 expression was significantly reduced. Decreased expression levels of Spire2 were also observed in kainic acid (KA) and pentylenetetrazole (PTZ) animal models. In the KA and PTZ models, Spire2-knockdown mice showed significantly increased seizures and shortened intervals between seizures, with a tendency to increase seizure duration. In contrast, Spire2-overexpressing mice showed reduced numbers of spontaneous seizures. In conclusion, this study revealed a significantly decreased expres-sion of Spire2 in the brain tissues of epileptic individuals and an inhibitory role for this protein in the development of epilepsy. In addition, knockdown of Spire2 aggravated abnormal firing in epileptic mice, while its overexpres-sion had the opposite effect. These findings provide new insights into the mechanism of epileptogenesis.(c) 2022 IBRO. Published by Elsevier Ltd. All rights reserved."

基金机构：Science and Technology Million Project of Inner Mongolia Medical University; Natural Science Foundation of Shanxi Province; [YKD2017KJBW (LH) 009]; [20210302123486]

基金资助正文：Funding This work was supported by grants from Science and Technology Million Project of Inner Mongolia Medical University (Grant No YKD2017KJBW (LH) 009) and Natural Science Foundation of Shanxi Province (grant number 20210302123486) .