Neural Regeneration Research ›› 2021, Vol. 16 ›› Issue (12): 2542-2548.doi: 10.4103/1673-5374.313054

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Inhibitor of DNA binding 2 accelerates nerve regeneration after sciatic nerve injury in mice

Zhong-Hai Huang1, Ai-Ying Feng1, Jing Liu1, Libing Zhou1, Bing Zhou2, *, Panpan Yu1, *   

  1. 1Guangdong-Hong Kong-Macau Institute of Central Nervous System Regeneration; Ministry of Education Joint International Research Laboratory of Central Nervous System Regeneration, Jinan University, Guangzhou, Guangdong Province, China; 2Interdisciplinary Innovation Institute of Medicine and Engineering, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, China
  • Online:2021-12-15 Published:2021-05-17
  • Contact: Panpan Yu, PhD, yupanpan21@jnu.edu.cn; Bing Zhou, PhD, bingzh@buaa.edu.cn.
  • Supported by:
     This work was supported by the National Natural Science Foundation of China, Nos. 82071369 (to PY) and 81971198 (to BZ); Guangdong grant ‘Key Technologies for Treatment of Brain Disorders’ of China, No. 2018B030332001 (to LZ and PY); Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology, China, No. 20200730090 (to LZ); the Natural Science Foundation of Beijing of China, No. 7192103 (to BZ); and the Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory of China, No. 2018GZR0201006 (to PY).

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Abstract: Inhibitor of DNA binding 2 (Id2) can promote axonal regeneration after injury of the central nervous system. However, whether Id2 can promote axonal regeneration and functional recovery after peripheral nerve injury is currently unknown. In this study, we established a mouse model of bilateral sciatic nerve crush injury. Two weeks before injury, AAV9-Id2-3×Flag-GFP was injected stereotaxically into the bilateral ventral horn of lumbar spinal cord. Our results showed that Id2 was successfully delivered into spinal cord motor neurons projecting to the sciatic nerve, and the number of regenerated motor axons in the sciatic nerve distal to the crush site was increased at 2 weeks after injury, arriving at the tibial nerve and reinnervating a few endplates in the gastrocnemius muscle. By 1 month after injury, extensive neuromuscular reinnervation occurred. In addition, the amplitude of compound muscle action potentials of the gastrocnemius muscle was markedly recovered, and their latency was shortened. These findings suggest that Id2 can accelerate axonal regeneration, promote neuromuscular reinnervation, and enhance functional improvement following sciatic nerve injury. Therefore, elevating the level of Id2 in adult neurons may present a promising strategy for peripheral nerve repair following injury. The study was approved by the Experimental Animal Ethics Committee of Jinan University (approval No. 20160302003) on March 2, 2016.

Key words: axonal regeneration, functional recovery, inhibitor of DNA binding 2, motor neuron, neuromuscular junctions, peripheral nerve, reinnervation, sciatic nerve injury

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