Frizzled 6 mutation regulates reserpine-induced depression-like behavior and Wnt signaling pathway in mice.
Eur J Pharmacol
; 957: 175996, 2023 Oct 15.
Article
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| MEDLINE
| ID: mdl-37597646
ABSTRACT
BACKGROUND:
Frizzled 6 (Fzd6) is involved in the development of various disorders; however, its role in the etiology of depression remains unclear. We aimed to determine the potential regulatory mechanisms of Fzd6 as a Wnt receptor in depression.METHODS:
Mice were divided into four groups wild-type control (Fzd6WT-control), Fzd6 mutant control (Fzd6Q152E-control), wild-type reserpine (Fzd6WT-reserpine), and Fzd6 mutant reserpine (Fzd6Q152E-reserpine). Reserpine (0.5 mg/kg) was injected intraperitoneally for 10 days. Four behavioral experiments were performed to assess the effects of Fzd6Q152E on depression-like behaviors in the reserpine-treated mice. Blood samples were collected for an enzyme-linked immunosorbent assay (ELISA). Gene expression in the hippocampus was quantified using quantitative real-time polymerase chain reaction (qRT-PCR), and protein expression levels in the hippocampus were identified using western blotting.RESULTS:
The Fzd6 mutation affected reserpine-induced depression-like behavioral changes in mice. ELISA revealed significantly reduced serum levels of 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), and norepinephrine in both Fzd6Q152E-reserpine and Fzd6WT-reserpine mice, with a more pronounced decrease in Fzd6Q152E-reserpine mice, especially in norepinephrine expression. The qRT-PCR results showed significantly decreased Fzd6 expression in Fzd6Q152E-reserpine mice and altered expression of Dkk2, Gsk-3ß, Lrp6, Wnt2, Wnt3, and Wnt3a in the Wnt pathway. Western blotting revealed decreased Fzd6 protein expression in Fzd6Q152E-control mice compared to Fzd6WT-control mice, whereas Fzd6 protein expression was restored in Fzd6Q152E-reserpine mice, and Gsk-3ß expression was significantly changed.CONCLUSION:
Fzd6 potentially influences reserpine-induced depressive behavioral changes and serum depressive factor alterations and modulates the expression of the Wnt signaling pathway in the hippocampus of depressed mice.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Depresión
/
Vía de Señalización Wnt
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2023
Tipo del documento:
Article
País de afiliación:
China