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Deficiency of microglial Hv1 channel is associated with activation of autophagic pathway and ROS production in LPC-induced demyelination mouse model
- Source :
- Journal of Neuroinflammation, Vol 17, Iss 1, Pp 1-12 (2020), Journal of Neuroinflammation
- Publication Year :
- 2020
- Publisher :
- BMC, 2020.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 17422094
- Volume :
- 17
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Neuroinflammation
- Accession number :
- edsair.doi.dedup.....fb4f7b9516863a3a676eaa4437d4c6dc