The voltage-gated proton channel Hv1 promotes microglia-astrocyte communication and neuropathic pain after peripheral nerve injury

Molecular Brain

Heejin Jeong¹  Seog Bae Oh¹  Shashank Ganatra²  Przemyslaw Peter McEwan²  Yi Ren²  Jiaying Zheng³  Jiyun Peng³  Long-Jun Wu³  Min-Hee Yi³  Jason R. Richardson⁴  Gongxiong Wu⁵ 

[1] Dental Research Institute and Department of Neurobiology and Physiology, School of Dentistry, Seoul National University;Department of Cell Biology and Neuroscience, Rutgers University;Department of Neurology, Mayo Clinic;Departments of Environmental Health Sciences, Florida International University;One Harvard Street Institute of Health;

关键词: Microglia;    Hv1 proton channel;    Hvcn1;    Reactive oxygen species;    IFN-γ;    Microglia-astrocyte interaction;   

DOI  :  10.1186/s13041-021-00812-8

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown