期刊
MOLECULAR BRAIN
卷 14, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13041-021-00812-8
关键词
Microglia; Hv1 proton channel; Hvcn1; Reactive oxygen species; IFN-gamma; Microglia-astrocyte interaction; Peripheral nerve injury; Neuropathic pain
资金
- National Institutes of Health [R01NS110825, R01NS088627]
- National Research Foundation of Korea from Korean government MSIT (Ministry of Science and ICT) [NRF-2017M3C7A1025602, 2018R1A5A2024418, 2021R1A2C3003334]
- National Research Foundation of Korea [2018R1A5A2024418, 2021R1A2C3003334] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The Hv1 proton channel in spinal microglia plays a crucial role in the development of neuropathic pain, with Hv1 deficiency potentially reducing pain hypersensitivities by affecting ROS production and astrocyte activation. This study suggests Hv1-dependent microglia-astrocyte communication is important in pain hypersensitivities and identifies Hv1 as a novel therapeutic target for alleviating neuropathic pain.
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-gamma 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-gamma 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据