CXCR5 Regulates Neuronal Polarity Development and Migration in the Embryonic Stage via F-Actin Homeostasis and Results in Epilepsy-Related Behavior

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外文摘要：Epilepsy is a common,chronic neurological disorder that has been associated with impaired neurode-velopment and immunity.The chemokine receptor CXCR5 is involved in seizures via an unknown mechanism.Here,we first determined the expression pattern and distribu-tion of the CXCR5 gene in the mouse brain during differ-ent stages of development and the brain tissue of patients with epilepsy.Subsequently,we found that the knockdown of CXCR5 increased the susceptibility of mice to pentylene-tetrazol-and kainic acid-induced seizures,whereas CXCR5 overexpression had the opposite effect.CXCR5 knockdown in mouse embryos via viral vector electrotransfer negatively influenced the motility and multipolar-to-bipolar transition of migratory neurons.Using a human-derived induced an in vitro multipotential stem cell neurodevelopmental model,we determined that CXCR5 regulates neuronal migration and polarization by stabilizing the actin cytoskeleton during various stages of neurodevelopment.Electrophysiological experiments demonstrated that the knockdown of CXCR5 induced neuronal hyperexcitability,resulting in an increased number of seizures.Finally,our results suggested that CXCR5 deficiency triggers seizure-related electrical activ-ity through a previously unknown mechanism,namely,the disruption of neuronal polarity.

外文关键词：

EpilepsyCXCR5Embryonic neurogenesisPluripotent stem cellsIntrauterine electroporationF-actinNeuronal polarityNeuronal migration

作者：

Zhijuan Zhang、Hui Zhang、Ana Antonic-Baker、Patrick Kwan、Yin Yan、Yuanlin Ma

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作者单位：

Department of Neurology,Chongqing Key Laboratory of Neurology,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China

Department of Neuroscience,Central Clinical School,Monash University,Melbourne,Australia

Chongqing Emergency Medical Center,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China

基金：

Science and Technology Program of Chongqing of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of China

项目编号：

cstc2018jcyjAX0038190132282271497

出版年：

2023

DOI：

10.1007/s12264-023-01087-w

神经科学通报(英文版)

中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD

影响因子：0.741

ISSN：1673-7067

年,卷(期)：2023.39(11)

参考文献量33