Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People's Republic of China.
Department of Neurology, Second Affiliated Hospital of University of South China, Hengyang, 421001, Hunan, People's Republic of China.
J Neuroinflammation. 2020 Nov 6;17(1):333. doi: 10.1186/s12974-020-02020-y.
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.
多发性硬化症（MS）是一种中枢神经系统的免疫介导的脱髓鞘疾病。小胶质细胞的激活参与了髓鞘丢失的发病机制。
本研究通过研究溶血磷脂酰胆碱（LPC）介导的脱髓鞘后活性氧（ROS）产生在调节脱髓鞘和小胶质细胞激活中的 Hv1 作用，探讨了自噬在这个过程中的作用。
采用两点 LPC 注射到胼胝体的方法建立脱髓鞘模型。采用 LFB 染色、免疫荧光、Western blot 和电镜观察脱髓鞘的严重程度。通过免疫荧光和 Western blot 检测小胶质细胞表型和自噬。采用 Morris 水迷宫测试空间学习和记忆能力。
我们发现 LPC 介导的髓鞘损伤减少了 Hv1 缺乏。此外，我们发现脱髓鞘区域的小胶质细胞 ROS 和自噬增加，这也被 Hv1 敲除所抑制。
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。
