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Role of microtubule dynamics in Wallerian degeneration and nerve regeneration after peripheral nerve injury
Authors:Jingmin Liu  Lixia Li  Ying Zou  Lanya Fu  Xinrui Ma  Haowen Zhang  Yizhou Xu  Jiawei Xu  Jiaqi Zhang  Mi Li  Xiaofang Hu  Zhenlin Li  Xianghai Wang  Hao Sun  Hui Zheng  Lixin Zhu  Jiasong Guo
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.

Chinese Library Classification No. R446; R745; Q245
Keywords:
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