title: Autophagy Promotes Peripheral Nerve Regeneration and Motor Recovery Following Sciatic Nerve Crush Injury in Rats.
abstract: Autophagy maintains cellular homeostasis by stimulating the lysosomal degradation of cytoplasmic structures, including damaged organelles and dysfunctional proteins. The role of autophagy in the renewal and regeneration of injured peripheral nerves remains poorly understood. The current study investigated the role of autophagy in peripheral nerve regeneration and motor function recovery following sciatic nerve crush injury in rats by stimulating or suppressing autophagy and detecting the presence of autophagosomes and LC3-II expression by electron microscopy and Western blotting, respectively. Neurobehavioral function was tested by CatWalk gait analysis 1, 2, 3, and 6 weeks after injury, and the expression of neurofilament (NF)-200 and myelin basic protein (MBP) at the injury site was examined by immunocytochemistry. Apoptosis at the lesion site was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Treatment of injured rats with the autophagy inducer rapamycin increased the number of autophagosomes and LC3-II expression while reducing the number of apoptotic cells at the lesion; this was associated with an upregulation of MBP and NF-200 expression and increased motor function recovery as compared to sham-operated rats and those that were subjected to crush injury but untreated. The opposite effects were observed in rats treated with the autophagy inhibitor 3-methyladenine. These data indicate that the modulation of autophagy in peripheral nerve injury could be an effective pharmacological approach to promote nerve regeneration and reestablish motor function.
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, 183 West Guangzhou, Avenue, Guangzhou, 510630, China.
authors.forename: Hai-Cheng
authors.initials: HC
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, 183 West Guangzhou, Avenue, Guangzhou, 510630, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, 183 West Guangzhou, Avenue, Guangzhou, 510630, China.
authors.forename: Hai-Xing
authors.initials: HX
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, 183 West Guangzhou, Avenue, Guangzhou, 510630, China.
authors.forename: Sheng-Fa
authors.initials: SF
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, 183 West Guangzhou, Avenue, Guangzhou, 510630, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, 183 West Guangzhou, Avenue, Guangzhou, 510630, China.
authors.forename: Tian-Yun
authors.initials: TY
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, 183 West Guangzhou, Avenue, Guangzhou, 510630, China. lcxdoc@163.com.
authors.forename: Chuan-Xiang
authors.initials: CX
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D005260:Female; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009068:Movement; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009416:Nerve Regeneration; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism / Q000502:physiology
chemical_list: D008869:Microtubule-Associated Proteins; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; C526109:Anxa3 protein, rat; C051774:neurofilament protein H
keywords: Autophagy; MTOR; Peripheral nerve regeneration; Rapamycin; Rat