ß-hydroxybutyrate reduces reinstatement of cocaine conditioned place preference through hippocampal CaMKII-α ß-hydroxybutyrylation.
Cell Rep
; 41(9): 111724, 2022 11 29.
Article
em En
| MEDLINE
| ID: mdl-36450263
ABSTRACT
Studies have shown the therapeutic effects of a ketogenic diet (KD) on epilepsy, but the effect of a KD on drug reinstatement is largely unclear. This study aims to investigate whether KD consumption possesses therapeutic potential for cocaine reinstatement and the molecular mechanism. We find that a KD significantly reduces cocaine-induced reinstatement in mice, which is accompanied by a markedly elevated level of ß-hydroxybutyrate (ß-OHB), the most abundant ketone body, in the hippocampus. The underlying mechanism is that ß-OHB posttranslationally modifies CaMKII-α with ß-hydroxybutyrylation, resulting in significant inhibition of T286 autophosphorylation and downregulation of CaMKII activity. Collectively, our results reveal that ß-hydroxybutyrylation is a posttranslational modification of CaMKII-α that plays a critical role in mediating the effect of KD consumption in reducing cocaine reinstatement.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cocaína
/
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina
Limite:
Animals
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China