Huang Hai-Cheng, Chen Li, Zhang Hai-Xing, Li Sheng-Fa, Liu Pei, Zhao Tian-Yun, Li Chuan-Xiang
Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, 183 West Guangzhou, Avenue, Guangzhou, 510630, China.
J Mol Neurosci. 2016 Apr;58(4):416-23. doi: 10.1007/s12031-015-0672-9. Epub 2016 Jan 7.
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.
自噬通过刺激细胞质结构（包括受损细胞器和功能失调蛋白质）的溶酶体降解来维持细胞稳态。自噬在受损周围神经的更新和再生中的作用仍知之甚少。本研究通过刺激或抑制自噬，并分别通过电子显微镜和蛋白质免疫印迹法检测自噬体的存在和LC3-II的表达，来研究自噬在大鼠坐骨神经挤压伤后周围神经再生和运动功能恢复中的作用。在损伤后1、2、3和6周，通过CatWalk步态分析测试神经行为功能，并通过免疫细胞化学检查损伤部位神经丝（NF）-200和髓鞘碱性蛋白（MBP）的表达。通过末端脱氧核苷酸转移酶dUTP缺口末端标记法测定损伤部位的细胞凋亡。用自噬诱导剂雷帕霉素治疗受伤大鼠可增加自噬体数量和LC3-II表达，同时减少损伤部位的凋亡细胞数量；与假手术大鼠和遭受挤压伤但未治疗的大鼠相比，这与MBP和NF-200表达上调以及运动功能恢复增加有关。在用自噬抑制剂3-甲基腺嘌呤治疗的大鼠中观察到相反的效果。这些数据表明，调节周围神经损伤中的自噬可能是促进神经再生和重建运动功能的一种有效药理学方法。
