Inhibition of the microglial voltage-gated proton channel 1 channel ameliorates diabetes-associated cognitive dysfunction by regulating axon demyelination
Year: 2025
Type: article
Abstract: BACKGROUND: Diabetes is associated with increased cognitive decline and dementia due to the loss of myelinated nerve fiber function, which is linked to oligodendrocyte dysfunction. The voltage-gated proton channel 1 (Hv1) is important for the cellular proton extrusion machinery. However, its role in regulating diabetes-induced cognitive dysfunction is unclear. AIM: To investigate the role of Hv1 in cognitive impairment induced by diabetes and its potential mechanisms, focusing on neuroinflammation, oligodendrocyte apoptosis, and axonal demyelination. METHODS: behavioral tests and neuroinflammation using immunofluorescence. Oligodendrocyte apoptosis was assessed with the terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay, and axonal demyelination was analyzed using electron microscopy. RESULTS: Hv1 expression was significantly increased in the corpus callosum of diabetic mice. Hv1 KO alleviated cognitive impairment, reduced oligodendrocyte apoptosis, and decreased the expression of inflammatory factors, including interleukin-1 and tumor necrosis factor-α, in diabetic mice. Electron microscopy revealed a reduction in myelin thickness and an increased g-ratio in diabetic mice, which were reversed by Hv1 KO. CONCLUSION: Hv1 plays a role in diabetes-induced cognitive dysfunction by modulating neuroinflammation and myelin integrity. Hv1 KO demonstrates therapeutic potential in mitigating diabetes-related cognitive decline and associated complications.
Source: World Journal of Psychiatry
Authors: Chun-Yu Li, Shu-Jun Zhang, Jia-Lu Xu, Yan Yang, Zhi-Xuan Zeng, De-Lin Ma
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4407925013