CXCR5 Regulates Neuronal Polarity Development and Migration in the Embryonic Stage via F-Actin Homeostasis and Results in Epilepsy-Related Behavior.
10.1007/s12264-023-01087-w
- Author:
Zhijuan ZHANG
1
;
Hui ZHANG
1
;
Ana ANTONIC-BAKER
2
;
Patrick KWAN
3
;
Yin YAN
4
;
Yuanlin MA
5
Author Information
1. Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
2. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia.
3. Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. patrick.kwan@monash.edu.
4. Chongqing Emergency Medical Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. 19280364@qq.com.
5. Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. mayuanlin2010@bjmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
CXCR5;
Embryonic neurogenesis;
Epilepsy;
F-actin;
Intrauterine electroporation;
Neuronal migration;
Neuronal polarity;
Pluripotent stem cells
- MeSH:
Animals;
Humans;
Mice;
Actin Cytoskeleton/metabolism*;
Actins/metabolism*;
Epilepsy/metabolism*;
Neurons/metabolism*;
Receptors, CXCR5/metabolism*;
Seizures/metabolism*
- From:
Neuroscience Bulletin
2023;39(11):1605-1622
- CountryChina
- Language:English
-
Abstract:
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.
