Deng Binbin, Lv Wenjing, Duan Weisong, Liu Yakun, Li Zhongyao, Ma Yanqin, Zhang Guisen, Song Xueqin, Cui Can, Qi Xiaoming, Li Yuan, Li Chunyan
Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, China.
Institute of Cardiocerebrovascular Disease, Shijiazhuang, China.
Cell Physiol Biochem. 2018;46(6):2358-2372. doi: 10.1159/000489627. Epub 2018 May 4.
Myelination, degeneration and regeneration are implicated in crucial responses to injury in the peripheral nervous system. Considering the progression of amyotrophic lateral sclerosis (ALS), we used the superoxide dismutase 1 (SOD1)-G93A transgenic mouse model of ALS to investigate the effects of mutant SOD1 on the peripheral nerves.
Changes in peripheral nerve morphology were analyzed in SOD1 mutant mice at various stages of the disease by toluidine blue staining and electron microscopy (EM). Schwann cell proliferation and recruitment of inflammatory factors were detected by immunofluorescence staining and quantitative reverse transcription PCR and were compared between SOD1 mutant mice and control mice. Furthermore, western blotting (WB) and TUNEL staining were used to investigate axonal damage and Schwann cell survival in the sciatic nerves of mice in both groups.
An analysis of the peripheral nervous system in SOD1-G93A mice revealed the following novel features: (i) Schwann cells and axons in mutant mice underwent changes that were similar to those seen in the control mice during the early development of peripheral nerves. (ii) The peripheral nerves of SOD1-G93A mice developed progressive neuropathy, which presented as defects in axons and myelin, leading to difficulty in walking and reduced locomotor capacity at a late stage of the disease. (iii) Macrophages were recruited and accumulated, and nerve injury and a deficit in the blood-nerve barrier were observed. (iv) Proliferation and the inflammatory micro-environment were inhibited, which impaired the regeneration and remyelination of axons after crush injury in the SOD1-G93A mice.
The mutant human SOD1 protein induced axonal and myelin degeneration during the progression of ALS and participated in axon remyelination and regeneration in response to injury.
髓鞘形成、退变和再生与周围神经系统对损伤的关键反应有关。考虑到肌萎缩侧索硬化症（ALS）的进展，我们使用超氧化物歧化酶1（SOD1）-G93A转基因ALS小鼠模型来研究突变型SOD1对周围神经的影响。
通过甲苯胺蓝染色和电子显微镜（EM）分析疾病不同阶段SOD1突变小鼠周围神经形态的变化。通过免疫荧光染色和定量逆转录PCR检测雪旺细胞增殖和炎症因子募集情况，并在SOD1突变小鼠和对照小鼠之间进行比较。此外，采用蛋白质免疫印迹法（WB）和TUNEL染色研究两组小鼠坐骨神经中的轴突损伤和雪旺细胞存活情况。
对SOD1-G93A小鼠周围神经系统的分析揭示了以下新特征：（i）突变小鼠中的雪旺细胞和轴突在周围神经早期发育过程中经历了与对照小鼠相似的变化。（ii）SOD1-G93A小鼠的周围神经出现进行性神经病变，表现为轴突和髓鞘缺陷，导致疾病后期行走困难和运动能力下降。（iii）巨噬细胞被募集并积聚，观察到神经损伤和血-神经屏障缺陷。（iv）增殖和炎症微环境受到抑制，这损害了SOD1-G93A小鼠挤压伤后轴突的再生和髓鞘再生。
突变型人SOD1蛋白在ALS进展过程中诱导轴突和髓鞘退变，并参与损伤后轴突的髓鞘再生和再生过程。
