Deficiency of microglial Hv1 channel is associated with activation of autophagic pathway and ROS production in LPC-induced demyelination mouse model
| Autor: | Luo Qi Zhou, Lin Lin Yang, Dai Shi Tian, Ya ling Duan, Ke Bin Zhan, Long Jun Wu, Dale B. Bosco, Man Chen, Sha Bei Xu, Chuan Qin, Zi Wei Hu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Immunology Morris water navigation task Ion Channels lcsh:RC346-429 Cellular and Molecular Neuroscience Myelin chemistry.chemical_compound Mice Western blot Neuroinflammation medicine Autophagy Animals lcsh:Neurology. Diseases of the nervous system Mice Knockout Microglia medicine.diagnostic_test Chemistry General Neuroscience Multiple sclerosis Research Lysophosphatidylcholines ROS medicine.disease Cell biology Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Lysophosphatidylcholine Neurology Female Demyelination Reactive Oxygen Species Demyelinating Diseases |
| Zdroj: | Journal of Neuroinflammation, Vol 17, Iss 1, Pp 1-12 (2020) Journal of Neuroinflammation |
| ISSN: | 1742-2094 |
| Popis: | Background 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. Objective 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. Methods 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. Results 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. Conclusion These results suggested that microglial Hv1 deficiency ameliorates demyelination through inhibition of ROS-mediated autophagy and microglial phenotypic transformation. |
| Databáze: | OpenAIRE |
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