Removing a specific microglial proton channel reduces nerve damage and memory loss in diabetic mice

Hv1 is upregulated in the corpus callosum of diabetic mice, and its knockout improves working memory.

• Knockout of Hv1 reduces the production of inflammatory markers interleukin-1β and tumor necrosis factor alpha by microglia.
• Decreased apoptosis of oligodendrocyte progenitor cells was observed in Hv1 knockout mice.
• Myelin thickness and g-ratio remained within normal limits in knockout mice, indicating preserved myelin integrity.
• Knockdown of Hv1 mitigated interleukin-1β secretion and suppressed markers associated with ferroptosis.
• Findings suggest a potential role for an Hv1-reactive oxygen species-glucose-regulated protein 78 axis in diabetic demyelination.

Simplified