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

作者全名："Zhang, Zhijuan; Zhang, Hui; Antonic-Baker, Ana; Kwan, Patrick; Yan, Yin; Ma, Yuanlin"

作者地址："[Zhang, Zhijuan; Zhang, Hui; Kwan, Patrick; Ma, Yuanlin] Chongqing Med Univ, Dept Neurol, Chongqing Key Lab Neurol, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Yan, Yin] Chongqing Med Univ, Chongqing Emergency Med Ctr, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Antonic-Baker, Ana; Kwan, Patrick] Monash Univ, Cent Clin Sch, Dept Neurosci, Melbourne, Australia"

通信作者："Kwan, P; Ma, YL (通讯作者)，Chongqing Med Univ, Dept Neurol, Chongqing Key Lab Neurol, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Yan, Y (通讯作者)，Chongqing Med Univ, Chongqing Emergency Med Ctr, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Kwan, P (通讯作者)，Monash Univ, Cent Clin Sch, Dept Neurosci, Melbourne, Australia."

来源：NEUROSCIENCE BULLETIN

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001029869900002

JCR分区：Q1

影响因子：5.9

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Epilepsy; CXCR5; Embryonic neurogenesis; Pluripotent stem cells; Intrauterine electroporation; F-actin; Neuronal polarity; Neuronal migration

摘要："Epilepsy is a common, chronic neurological disorder that has been associated with impaired neurodevelopment and immunity. The chemokine receptor CXCR5 is involved in seizures via an unknown mechanism. Here, we first determined the expression pattern and distribution of the CXCR5 gene in the mouse brain during different 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 pentylenetetrazol- 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 activity through a previously unknown mechanism, namely, the disruption of neuronal polarity."

基金机构："Science and Technology Program of Chongqing of China [cstc2018jcyjAX003]; National Natural Science Foundation of China [81901322, 82271497]"

基金资助正文："AcknowledgementsThis work was supported by grants from the Science and Technology Program of Chongqing of China (cstc2018jcyjAX003), and the National Natural Science Foundation of China (81901322 and 82271497)."