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Axonal regeneration in early stages of sciatic nerve crush injury is enhanced by α7nAChR in rats

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Abstract

This study investigated the role of alpha 7 nicotinic acetylcholine receptor (α7nAChR) in axonal regeneration after crush injury to the rat sciatic nerve. The time course of α7nAChR expression following injury was assessed by immunohistochemistry and western blotting, and local inflammation, as indicated by the expression of tumor necrosis factor (TNF)-α, was detected by enzyme-linked immunosorbent assay. Axonal regeneration was evaluated by the pinch-test, morphometric analysis, and by measuring growth-associated protein 43 expressions. Local α7nAChR expression increased on day 1, peaked on day 3, and remained elevated on day 5 following nerve injuries. Prominent α7nAChR immunoreactivity was observed in Schwann cells, endothelial cells of the capillaries, and a small number of inflammatory cells. Application of the selective α7nAChR agonist PNU-282987 decreased TNF-α level and enhanced axonal regeneration, but this effect was blocked by concomitant treatment with methyllycaconitine, a α7nAChR antagonist. The results indicate that the local expression of α7nAChR is increased during the early stages of sciatic nerve injury, and application of a α7nAChR agonist promotes axonal regeneration by suppression of TNF-α-mediated inflammation. The α7nAChR can act as a neuroprotective agent and α7nAChR activation may be a useful therapeutic strategy to treat peripheral nerve injury.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China

    Dewei Wang, Xuming Wang, Shuo Geng & Zhenggang Bi

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  1. Dewei Wang
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  2. Xuming Wang
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  3. Shuo Geng
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  4. Zhenggang Bi
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Correspondence to Zhenggang Bi.

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Wang, D., Wang, X., Geng, S. et al. Axonal regeneration in early stages of sciatic nerve crush injury is enhanced by α7nAChR in rats. Mol Biol Rep 42, 603–609 (2015). https://doi.org/10.1007/s11033-014-3805-2

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  • DOI: https://doi.org/10.1007/s11033-014-3805-2

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