Effect of Notch1 gene on remyelination in multiple sclerosis in mouse models of acute demyelination
Effect of Notch1 gene on remyelination in multiple sclerosis in mouse models of acute demyelination
复制标题
Notch1基因对多发性硬化小鼠急性脱髓鞘模型髓鞘再生的影响
DOI：
10.1002/jcb.27197
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发表时间：
2018-11-01
影响因子：
4
通讯作者：
Bai, Xiao-Li
中科院分区：
文献类型：
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作者：
Fan, Hua;Zhao, Jie-Gang;Bai, Xiao-Li
本研究旨在探讨Notch1基因在多发性硬化症(MS)髓鞘再生中的作用。建立小鼠急性脱髓鞘模型，随机分为铜酮(CPZ)组、CPZ+siRNA-Notch1组(SiNotch1)和CPZ+siRNA阴性对照(NC)组。另设3组(对照组、对照组+siNotch1、对照组+siRNA NC)。观察小鼠转鼓中体重和维持时间的变化。Western印迹分析Notch信号通路和少突胶质细胞分化相关蛋白在小鼠胼胝体中的表达。模型建立后，CPZ脱髓鞘小鼠体重减轻。在修复期间，小鼠的平衡能力和运动能力都得到了恢复，尤其是注射siNotch1质粒的小鼠。造模后有髓轴突数量减少。与CPZ和CPZ siRNA NC组相比，CPZ+siNotch1组的早熟OL数量减少，成熟OL数量增加，少突胶质前体细胞和星形胶质细胞减少。与CPZ和CPZ+siRNA组相比，CPZ+siNotch1组Notch信号通路相关蛋白HES、Jagge-1表达降低，而OL相关转录因子Sox10表达增加，Id2表达降低。我们的研究提供了证据，表明抑制Notch1基因可以加速MS的重新髓鞘形成。
This study aims to explore the effects of Notch1 gene on remyelination in multiple sclerosis (MS). A mouse model of acute demyelination was successfully established and the model mice were grouped as cuprizone (CPZ) group, CPZ + small interfering RNA (siRNA)‐Notch1 (siNotch1) group, and CPZ + siRNA negative control (NC) group. Meanwhile, another 3 groups (control, control + siNotch1, and control + siRNA NC) were established in normal mice. The changes of weight and maintenance time in rotating drum of mice were observed. Western blot analysis for the protein expressions related to Notch signaling pathway and oligodendrocyte (OL) differentiation in the corpus callosum of the mice. After model establishment, the weight of CPZ‐induced demyelinated mice was decreased. During the repair period, the balance ability and movement of the mice was recovered, especially for those injected with siNotch1 plasmid. After model establishment, the number of myelinated axons was decreased. In comparison with the CPZ and CPZ siRNA NC groups, the CPZ + siNotch1 group had a decrease in the number of premature OLs, but increase in mature OLs, and a decrease in oligodendrocyte precursor cells and astrocytes. The expressions of proteins related to Notch signaling pathway, such as HES, Jagged‐1 were decreased in the CPZ + siNotch1 group in contrast to the CPZ and CPZ + siRNA groups, but the OL‐related transcription factor Sox10 was increased in the CPZ + siNotch1 group than in the CPZ + siRNA NC and CPZ groups, and Id2 was decreased. Our study provided evidence that the inhibition of Notch1 gene could accelerate remyelination in MS.