The voltage-gated proton channel Hv1 promotes microglia-astrocyte communication and neuropathic pain after peripheral nerve injury
Autor: | Yi Ren, Jason R. Richardson, Min Hee Yi, Long Jun Wu, Jiyun Peng, Shashank Ganatra, Jiaying Zheng, Seog Bae Oh, Gongxiong Wu, Heejin Jeong, Przemyslaw Peter McEwan |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
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 |
Zdroj: | Molecular Brain Molecular Brain, Vol 14, Iss 1, Pp 1-18 (2021) |
ISSN: | 1756-6606 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |