Neural Regeneration Research ›› 2022, Vol. 17 ›› Issue (3): 673-681.doi: 10.4103/1673-5374.320997

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Role of microtubule dynamics in Wallerian degeneration and nerve regeneration after peripheral nerve injury

Jingmin Liu1, 2, Lixia Li1, 2, Ying Zou1, 2, Lanya Fu1, 2, Xinrui Ma1, 2, Haowen Zhang1, 2, Yizhou Xu1, 2, 3, Jiawei Xu1, 2, Jiaqi Zhang1, 2, Mi Li1, 2, Xiaofang Hu1, 2, Zhenlin Li1, 2, Xianghai Wang1, 2, 4, Hao Sun4, Hui Zheng4, Lixin Zhu3, Jiasong Guo1, 2, 3, 4, 5, *   

  1. 1Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province, China; 2Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong Province, China; 3Department of Spine Orthopedics, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, China; 4Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong Province, China; 5Key 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
  • Online:2022-03-15 Published:2021-10-15
  • Contact: Jiasong Guo, PhD, jiasongguo@smu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 82071386 (to JS), 81870982 (to JS) & 81571182 (to JS); the National Key Basic Research Program of China, No. 2014CB542202 (to JS); the Program for Changjiang Scholars and Innovative Research Team in University of China, No. IRT-16R37 (to JS); Key Research & Development Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory of China, No. 2018GZR110104008 (to HZ); Research Grant of Guangdong Province Key Laboratory of Psychiatric Disorders of China, No. N201904 (to JS); and Natural Science Foundation of Guangdong Province of China, No. 2017A030312009 (to JS).

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Abstract: Wallerian degeneration, the progressive disintegration of distal axons and myelin that occurs after peripheral nerve injury, is essential for creating a permissive microenvironment for nerve regeneration, and involves cytoskeletal reconstruction. However, it is unclear whether microtubule dynamics play a role in this process. To address this, we treated cultured sciatic nerve explants, an in vitro model of Wallerian degeneration, with the microtubule-targeting agents paclitaxel and nocodazole. We found that paclitaxel-induced microtubule stabilization promoted axon and myelin degeneration and Schwann cell dedifferentiation, whereas nocodazole-induced microtubule destabilization inhibited these processes. Evaluation of an in vivo model of peripheral nerve injury showed that treatment with paclitaxel or nocodazole accelerated or attenuated axonal regeneration, as well as functional recovery of nerve conduction and target muscle and motor behavior, respectively. These results suggest that microtubule dynamics participate in peripheral nerve regeneration after injury by affecting Wallerian degeneration. This study was approved by the Animal Care and Use Committee of Southern Medical University, China (approval No. SMU-L2015081) on October 15, 2015.

Key words: axon, demyelination, microtubule dynamics, nerve regeneration, nocodazole, paclitaxel, peripheral nerve injury, Schwann cell, Wallerian degeneration

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