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

Mi Li; Jiawei Xu; Ying Zou; Jialing Lu; Aiyue Ou; Xinrui Ma; Jiaqi Zhang; Yizhou Xu; Lanya Fu; Jingmin Liu; Xianghai Wang; Libing Zhou; Jiasong Guo

doi:10.4103/1673-5374.373657

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

Neural Regen Res. 2023 Dec;18(12):2757-2761. doi: 10.4103/1673-5374.373657.

Authors

Mi Li¹, Jiawei Xu¹, Ying Zou¹, Jialing Lu¹, Aiyue Ou¹, Xinrui Ma¹, Jiaqi Zhang¹, Yizhou Xu², Lanya Fu¹, Jingmin Liu¹, Xianghai Wang³, Libing Zhou⁴, Jiasong Guo⁵

Affiliations

¹ Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province, China.
² Department of Histology and Embryology, School of Basic Medical Sciences; Department of Spine Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
³ Department of Histology and Embryology, School of Basic Medical Sciences; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University; Key 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.
⁴ Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, Guangdong Province, China.
⁵ Department of Histology and Embryology, School of Basic Medical Sciences; Department of Spine Orthopedics, Zhujiang Hospital; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University; Key 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.

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 HB9^Cre+ mice with RhoA^flox/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.

Keywords: RhoA; brachial plexus; conditional knockout; degeneration; dendrites; motor neuron; peripheral nerve injury; regeneration; spinal cord; ventral horn.