Microglial voltage-gated proton channel 1 ablation in diabetic mice mitigates diabetes-driven demyelination and cognitive decline

doi:10.5498/wjp.v15.i9.109363

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Sep 19, 2025 (publication date) through Sep 5, 2025

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World Journal of Psychiatry

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2220-3206

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Psychiatry. Sep 19, 2025; 15(9): 109363
Published online Sep 19, 2025. doi: 10.5498/wjp.v15.i9.109363

Table 3 Clinical implications and future directions

Goal	Strategy	Readouts
Early intervention window	Hv1 inhibitors initiated at MRI-detected white matter changes or mild cognitive impairment	Diffusion MRI metrics; cognitive test scores
Enhanced remyelination	Combine Hv1 blockade with OPC-differentiation drugs (e.g., clemastine)	Myelin thickness; OPC maturation markers
Biomarker development	PET tracer or CFS assay for Hv1/IL-1β/GRP78	Imaging signal intensity; CFS levels
Broader disease scope	Evaluate Hv1 targeting in MS, Alzheimer’s, and stroke models	Disease-specific lesion load; behavioral assays

Hv1: Voltage-gated proton channel 1; MRI: Magnetic resonance imaging; OPC: Oligodendrocyte progenitor cell; PET: Positron emission tomography; CFS: Chronic fatigue syndrome; IL-1β: Interleukin-1β; GRP78: Glucose-regulated protein 78; MS: Mass spectrometry.

Citation: Li B. Microglial voltage-gated proton channel 1 ablation in diabetic mice mitigates diabetes-driven demyelination and cognitive decline. World J Psychiatry 2025; 15(9): 109363
URL: https://www.wjgnet.com/2220-3206/full/v15/i9/109363.htm
DOI: https://dx.doi.org/10.5498/wjp.v15.i9.109363