The antipsychotic chlorpromazine reduces neuroinflammation by inhibiting microglial voltage-gated potassium channels.

Autor: Lee HY; Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Republic of Korea., Lee Y; Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Republic of Korea., Chung C; Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Republic of Korea., Park SI; Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Republic of Korea.; Department of Physiology, Kangwon National University School of Medicine, Chuncheon, Republic of Korea., Shin HJ; Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, Republic of Korea., Joe EH; Department of Pharmacology, Ajou University School of Medicine, Suwon, Republic of Korea., Lee SJ; Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Republic of Korea., Kim DW; Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, Republic of Korea.; Department of Oral Anatomy & Developmental Biology, Kyung Hee University College of Dentistry, Seoul, Republic of Korea., Jo SH; Department of Physiology, Kangwon National University School of Medicine, Chuncheon, Republic of Korea., Choi SY; Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Republic of Korea.
Jazyk: angličtina
Zdroj: Glia [Glia] 2024 Oct 22. Date of Electronic Publication: 2024 Oct 22.
DOI: 10.1002/glia.24629
Abstrakt: Neuroinflammation, the result of microglial activation, is associated with the pathogenesis of a wide range of psychiatric and neurological disorders. Recently, chlorpromazine (CPZ), a dopaminergic D2 receptor antagonist and schizophrenia therapy, was proposed to exert antiinflammatory effects in the central nervous system. Here, we report that the expression of Kv1.3 channel, which is abundant in T cells, is upregulated in microglia upon infection, and that CPZ specifically inhibits these channels to reduce neuroinflammation. In the mouse medial prefrontal cortex, we show that CPZ lessens Kv1.3 channel activity and reduces proinflammatory cytokine production. In mice treated with LPS, we found that CPZ was capable of alleviating both neuroinflammation and depression-like behavior. Our findings suggest that CPZ acts as a microglial Kv1.3 channel inhibitor and neuroinflammation modulator, thereby exerting therapeutic effects in neuroinflammatory psychiatric/neurological disorders.
(© 2024 The Author(s). GLIA published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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