Multiple sclerosis (MS) is an immune-mediated demyelinated disease of the central nervous system. Activation of microglia is involved in the pathogenesis of myelin loss. This study is focused on the role of Hv1 in regulating demyelination and microglial activation through reactive oxygen species (ROS) production after lysophosphatidylcholine (LPC)-mediated demyelination. We also explored autophagy in this process. A model of demyelination using two-point LPC injection into the corpus callosum was established. LFB staining, immunofluorescence, Western blot, and electron microscopy were used to study the severity of demyelination. Microglial phenotype and autophagy were detected by immunofluorescence and Western blot. Morris water maze was used to test spatial learning and memory ability. We have identified that LPC-mediated myelin damage was reduced by Hv1 deficiency. Furthermore, we found that ROS and autophagy of microglia increased in the demyelination region, which was also inhibited by Hv1 knockout. These results suggested that microglial Hv1 deficiency ameliorates demyelination through inhibition of ROS-mediated autophagy and microglial phenotypic transformation.

中文翻译：

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在LPC诱导的脱髓鞘小鼠模型中，小胶质细胞Hv1通道的缺乏与自噬途径的激活和ROS的产生有关

多发性硬化症 (MS) 是一种免疫介导的中枢神经系统脱髓鞘疾病。小胶质细胞的激活参与髓鞘丢失的发病机制。本研究的重点是 Hv1 在通过溶血磷脂酰胆碱 (LPC) 介导的脱髓鞘后产生活性氧 (ROS) 来调节脱髓鞘和小胶质细胞活化中的作用。我们也在这个过程中探索了自噬。建立了胼胝体两点LPC注射脱髓鞘模型。使用 LFB 染色、免疫荧光、蛋白质印迹和电子显微镜来研究脱髓鞘的严重程度。通过免疫荧光和蛋白质印迹检测小胶质细胞表型和自噬。Morris水迷宫用于测试空间学习和记忆能力。我们已经确定 LPC 介导的髓鞘损伤因 Hv1 缺乏而减少。此外，我们发现脱髓鞘区域小胶质细胞的 ROS 和自噬增加，这也受到 Hv1 敲除的抑制。这些结果表明，小胶质细胞 Hv1 缺乏通过抑制 ROS 介导的自噬和小胶质细胞表型转化来改善脱髓鞘。