Abstract
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.
基金项目
Science and Technology Program of Chongqing of China(cstc2018jcyjAX003)
National Natural Science Foundation of China(81901322)
National Natural Science Foundation of China(82271497)
万方数据