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The voltage-gated proton channel Hv1 promotes microglia-astrocyte communication and neuropathic pain after peripheral nerve injury
- Source :
- Molecular Brain, Molecular Brain, Vol 14, Iss 1, Pp 1-18 (2021)
- Publication Year :
- 2021
- Publisher :
- BioMed Central, 2021.
-
Abstract
- Activation of spinal cord microglia contributes to the development of peripheral nerve injury-induced neuropathic pain. However, the molecular mechanisms underlying microglial function in neuropathic pain are not fully understood. We identified that the voltage-gated proton channel Hv1, which is functionally expressed in spinal microglia, was significantly increased after spinal nerve transection (SNT). Hv1 mediated voltage-gated proton currents in spinal microglia and mice lacking Hv1 (Hv1 KO) display attenuated pain hypersensitivities after SNT compared with wildtype (WT) mice. In addition, microglial production of reactive oxygen species (ROS) and subsequent astrocyte activation in the spinal cord was reduced in Hv1 KO mice after SNT. Cytokine screening and immunostaining further revealed that IFN-γ expression was compromised in spinal astrocytes in Hv1 KO mice. These results demonstrate that Hv1 proton channel contributes to microglial ROS production, astrocyte activation, IFN-γ upregulation, and subsequent pain hypersensitivities after SNT. This study suggests Hv1-dependent microglia-astrocyte communication in pain hypersensitivities and identifies Hv1 as a novel therapeutic target for alleviating neuropathic pain.
- Subjects :
- 0301 basic medicine
Voltage-gated proton channel
Cell Communication
Neuropathic pain
Models, Biological
p38 Mitogen-Activated Protein Kinases
Hv1 proton channel
Ion Channels
Microglia-astrocyte interaction
03 medical and health sciences
Cellular and Molecular Neuroscience
Interferon-gamma
0302 clinical medicine
Downregulation and upregulation
Hvcn1
Peripheral Nerve Injuries
medicine
Animals
RC346-429
Molecular Biology
IFN-γ
Cell Proliferation
Mice, Knockout
Microglia
business.industry
Research
Spinal cord
Up-Regulation
Enzyme Activation
Mice, Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
Spinal Cord
Spinal nerve
Peripheral nerve injury
Astrocytes
Neuralgia
Neurology. Diseases of the nervous system
business
Reactive Oxygen Species
Neuroscience
030217 neurology & neurosurgery
Astrocyte
Subjects
Details
- Language :
- English
- ISSN :
- 17566606
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Molecular Brain
- Accession number :
- edsair.doi.dedup.....8329e7df981790e457654d62596c5383