机构地区:[1]Department of Histology and Embryology,School of Basic Medical Sciences,Southern Medical University,Guangzhou,Guangdong Province,China [2]Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering,Southern Medical University,Guangzhou,Guangdong Province,China [3]Department of Spine Orthopedics,Zhujiang Hospital of Southern Medical University,Guangzhou,Guangdong Province,China [4]Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory),Guangzhou,Guangdong Province,China [5]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
出 处:《Neural Regeneration Research》2022年第3期673-681,共9页中国神经再生研究(英文版)
基 金: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);Natural Science Foundation of Guangdong Province of China,No.2017A030312009 (to JS)。
摘 要: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.SMUL2015081) on October 15,2015.
关 键 词:AXON DEMYELINATION microtubule dynamics nerve regeneration NOCODAZOLE PACLITAXEL peripheral nerve injury Schwann cell Wallerian degeneration
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