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

作　　者：Zhijuan Zhang Hui Zhang Ana Antonic‑Baker Patrick Kwan Yin Yan Yuanlin Ma 

机构地区：[1]Department of Neurology,Chongqing Key Laboratory of Neurology,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China [2]Chongqing Emergency Medical Center,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China [3]Department of Neuroscience,Central Clinical School,Monash University,Melbourne,Australia

出　　处：《Neuroscience Bulletin》2023年第11期1605-1622,共18页神经科学通报（英文版）

基　　金：supported by grants from the Science and Technology Program of Chongqing of China(cstc2018jcyjAX003);the National Natural Science Foundation of China(81901322 and 82271497).

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.

关 键 词：EPILEPSY CXCR5 Embryonic neurogenesis Pluripotent stem cells Intrauterine electroporation F-ACTIN Neuronal polarity Neuronal migration 

分 类 号：R749[医药卫生—神经病学与精神病学]