Inhibition of the microglial voltage-gated proton channel 1 channel ameliorates diabetes-associated cognitive dysfunction by regulating axon demyelination.

IF 3.9 4区 医学 Q1 PSYCHIATRY
Chun-Yu Li, Shu-Jun Zhang, Jia-Lu Xu, Yan Yang, Zhi-Xuan Zeng, De-Lin Ma
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引用次数: 0

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: A diabetes model was established by administering a high-fat diet and streptozotocin injections in mice. Hv1 knockout (KO) and wild-type mice were used to evaluate cognitive function via 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.

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自引率
6.50%
发文量
110
期刊介绍: The World Journal of Psychiatry (WJP) is a high-quality, peer reviewed, open-access journal. The primary task of WJP is to rapidly publish high-quality original articles, reviews, editorials, and case reports in the field of psychiatry. In order to promote productive academic communication, the peer review process for the WJP is transparent; to this end, all published manuscripts are accompanied by the anonymized reviewers’ comments as well as the authors’ responses. The primary aims of the WJP are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in psychiatry.
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