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 Aug 30, 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 2 Points for further consideration

Focus area	Action	Outcome measure
Longitudinal efficacy	Behavioral tests + diffusion MRI at 2, 8, 16 weeks	Memory scores; fractional anisotropy
Cell-type specificity	Generate CX3CR1-CreERT2 Hv1^flox/flox for microglia-only KO; compare GFAP-Cre astrocyte KO	Cytokine levels; OPC survival; g-ratio
Pharmacological proof-of-concept	Screen Hv1 inhibitors for IC₅₀, BBB penetration, and toxicity; test alone and with remyelinating agents	Patch-clamp IC₅₀; brain/plasma ratio; maze performance
Mechanistic clarification	pH imaging in microglia under hyperglycemia; Co-IP of Hv1 and NOX2	Intracellular pH; ROS assays; protein interaction

MRI: Magnetic resonance imaging; Hv1: Voltage-gated proton channel 1; CX3CR1: CX3C chemokine receptor 1; KO: Knockout; OPC: Oligodendrocyte progenitor cell; BBB: Blood-brain barrier; Co-IP: Co-immunoprecipitation; NOX2: NADPH oxidase 2; ROS: Reactive oxygen species.

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