中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (12): 2757-2761.doi: 10.4103/1673-5374.373657

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

运动神经元特异性RhoA敲除可延缓臂丛神经损伤后脊髓腹角树突的退变并促进其再生

  


  • 出版日期:2023-12-15 发布日期:2023-06-15
  • 基金资助:
    科技部中国脑计划(2022ZD0204701);国家自然科学基金项目(82071386&81870982)

Motor neuron-specific RhoA knockout delays degeneration and promotes regeneration of dendrites in spinal ventral horn after brachial plexus injury

Mi Li1, Jiawei Xu1, Ying Zou1, Jialing Lu1, Aiyue Ou1, Xinrui Ma1, Jiaqi Zhang1, Yizhou Xu1, 2, Lanya Fu1, Jingmin Liu1, #br# Xianghai Wang1, 3, 4, Libing Zhou5, Jiasong Guo1, 2, 3, 4, *   

  1. 1Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province, China; 2Department of Spine Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China; 3Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong Province, China; 4Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangzhou, Guangdong Province, China; 5Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, Guangdong Province, China
  • Online:2023-12-15 Published:2023-06-15
  • Contact: Jiasong Guo, PhD, jiasongguo@smu.edu.cn.
  • Supported by:
    This study was supported by the Ministry of Science and Technology China Brain Initiative Grant, No. 2022ZD0204701; and the National Natural Science Foundation of China, Nos. 82071386 & 81870982 (all to JG). 

摘要:

树突在神经传导通路中发挥着不可替代的作用,但其容易受到各种损伤。运动神经元在周围神经损伤后收缩,而当神经再支配时,树突则可重新延伸。RhoA是一种调节细胞骨架重建的重要开关分子,已成为促进神经元存活和轴突再生的靶点。然而,RhoA在树突退变和再生中的作用仍然未知。此次实验以HB9-Cre工具鼠和RhoA-Flox转基因小鼠杂交获得运动神经元RhoA条件性敲除小鼠,并在其成年后建立臂丛神经离断模型以及离断后神经修复模型。可见臂丛神经离断28d时,与Cre小鼠相比,RhoA条件性敲除小鼠脊髓腹角树突密度、树突复杂性以及结构完整性明显较轻。而在臂丛神经挤压后7和14d时,树突发生退变,而28-56d时有所恢复。与Cre小鼠相比,RhoA条件性敲除小鼠的树突密度、树突复杂性和结构完整性显著恢复。说明运动神经元中RhoA特异性敲除可削弱其树突退变,并促进周围神经损伤后树突的再生。

https://orcid.org/0000-0002-7885-2903 (Jiasong Guo) 

关键词:

RhoA, 条件性敲除, 运动神经元, 树突, 退变, 再生周围神经损伤, 脊髓, 腹角, 臂丛神经

Abstract: Dendrites play irreplaceable roles in the nerve conduction pathway and are vulnerable to various insults. Peripheral axotomy of motor neurons results in the retraction of dendritic arbors, and the dendritic arbor can be re-expanded when reinnervation is allowed. RhoA is a target that regulates the cytoskeleton and promotes neuronal survival and axon regeneration. However, the role of RhoA in dendrite degeneration and regeneration is unknown. In this study, we explored the potential role of RhoA in dendrites. A line of motor neuronal RhoA conditional knockout mice was developed by crossbreeding HB9Cre+ mice with RhoAflox/flox mice. We established two models for assaying dendrite degeneration and regeneration, in which the brachial plexus was transection or crush injured, respectively. We found that at 28 days after brachial plexus transection, the density, complexity, and structural integrity of dendrites in the ventral horn of the spinal cord of RhoA conditional knockout mice were slightly decreased compared with that in Cre mice. Dendrites underwent degeneration at 7 and 14 days after brachial plexus transection and recovered at 28–56 days. The density, complexity, and structural integrity of dendrites in the ventral horn of the spinal cord of RhoA conditional knockout mice recovered compared with results in Cre mice. These findings suggest that RhoA knockout in motor neurons attenuates dendrite degeneration and promotes dendrite regeneration after peripheral nerve injury.

Key words: brachial plexus, conditional knockout, degeneration, dendrites, motor neuron, peripheral nerve injury, regeneration, RhoA, spinal cord, ventral horn