The voltage-gated proton channel Hv1 contributes to neuronal injury and motor deficits in a mouse model of spinal cord injury

Madhuvika Murugan, Jiaying Zheng, Gongxiong Wu, Rochelle Mogilevsky, Xin Zheng, Peiwen Hu, Junfang Wu, Long Jun Wu

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Traumatic injury to the spinal cord initiates a series of pathological cellular processes that exacerbate tissue damage at and beyond the original site of injury. This secondary damage includes oxidative stress and inflammatory cascades that can lead to further neuronal loss and motor deficits. Microglial activation is an essential component of these secondary signaling cascades. The voltage-gated proton channel, Hv1, functionally expressed in microglia has been implicated in microglia polarization and oxidative stress in ischemic stroke. Here, we investigate whether Hv1 mediates microglial/macrophage activation and aggravates secondary damage following spinal cord injury (SCI). Following contusion SCI, wild-type (WT) mice showed significant tissue damage, white matter damage and impaired motor recovery. However, mice lacking Hv1 (Hv1−/−) showed significant white matter sparing and improved motor recovery. The improved motor recovery in Hv1−/− mice was associated with decreased interleukin-1β, reactive oxygen/ nitrogen species production and reduced neuronal loss. Further, deficiency of Hv1 directly influenced microglia activation as noted by decrease in microglia numbers, soma size and reduced outward rectifier K+ current density in Hv1−/− mice compared to WT mice at 7 d following SCI. Our results therefore implicate that Hv1 may be a promising potential therapeutic target to alleviate secondary damage following SCI caused by microglia/macrophage activation.

Original languageEnglish (US)
Article number143
JournalMolecular Brain
Volume13
Issue number1
DOIs
StatePublished - Dec 1 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Keywords

  • Hv1
  • Interleukin-1β
  • Microglia
  • Neuroinflammation
  • ROS
  • Spinal cord injury
  • Voltage-gated proton channel

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