Ji Yingxiao, Duan Weisong, Liu Yaling, Liu Yakun, Liu Chang, Li Yuanyuan, Wen Di, Li Zhongyao, Li Chunyan
Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People's Republic of China.
Neurological Laboratory of Hebei Province, Shijiazhuang, Hebei, 050000, People's Republic of China.
Neurosci Lett. 2018 Mar 6;668:1-6. doi: 10.1016/j.neulet.2017.12.062. Epub 2017 Dec 30.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease leading to paralysis and death within 3-5 years of its diagnosis. The SOD1G93A mouse is used extensively as an ALS animal model. Increasing evidence shows that non-neuronal cellscontribute to the pathogenesis and progression of ALS. Among them, many studies focus on microgliosis in the spinal cord (SC); while few on macrophage activation in the sciatic nerves. Substantial evidence shows that insulin-like growth factor 1 (IGF1) delays disease progression and increases the lifespan of SOD1G93A mice, and some studies indicate that IGF1 reduces inflammation in the SC of ALS mice. However, no studies have focused on the effect of IGF on sciatic nerve inflammation. Here, we find that ALS progression is characterized by increasing macrophage invasion and activation accompanied by significant TNF-α production in the sciatic nerve. Furthermore, IGF1 treatment and knockdown alleviate and aggravate these responses, respectively. Collectively, our findings show the first time that IGF1 has an anti-inflammatory effect in the sciatic nerves of SOD1G93A mice.
肌萎缩侧索硬化症（ALS）是一种进行性神经退行性疾病，在诊断后的3至5年内会导致瘫痪和死亡。SOD1G93A小鼠被广泛用作ALS动物模型。越来越多的证据表明，非神经元细胞参与了ALS的发病机制和进展。其中，许多研究聚焦于脊髓中的小胶质细胞增生；而对坐骨神经中巨噬细胞活化的研究较少。大量证据表明，胰岛素样生长因子1（IGF1）可延缓疾病进展并延长SOD1G93A小鼠的寿命，一些研究表明IGF1可减轻ALS小鼠脊髓中的炎症。然而，尚无研究关注IGF对坐骨神经炎症的影响。在此，我们发现ALS的进展表现为坐骨神经中巨噬细胞浸润和活化增加，并伴有大量肿瘤坏死因子-α的产生。此外，IGF1治疗和基因敲低分别减轻和加重了这些反应。总的来说，我们的研究首次表明IGF1对SOD1G93A小鼠的坐骨神经具有抗炎作用。
