The antipsychotic chlorpromazine reduces neuroinflammation by inhibiting microglial voltage-gated potassium channels.
Kv1.3 channel
chlorpromazine
microglia
neuroinflammation
psychiatric disease
Journal
Glia
ISSN: 1098-1136
Titre abrégé: Glia
Pays: United States
ID NLM: 8806785
Informations de publication
Date de publication:
22 Oct 2024
22 Oct 2024
Historique:
revised:
02
10
2024
received:
28
03
2024
accepted:
08
10
2024
medline:
22
10
2024
pubmed:
22
10
2024
entrez:
22
10
2024
Statut:
aheadofprint
Résumé
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.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Research Foundation of Korea
ID : 2016M3C7A1905481
Organisme : National Research Foundation of Korea
ID : 2018R1A5A2024418
Organisme : National Research Foundation of Korea
ID : 2020R1A2C1013958
Organisme : National Research Foundation of Korea
ID : 2020R1A2C3011464
Informations de copyright
© 2024 The Author(s). GLIA published by Wiley Periodicals LLC.
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