Lysosomal dysfunction is associated with NLRP3 inflammasome activation in chronic unpredictable mild stress-induced depressive mice.
Behav Brain Res
; 432: 113987, 2022 08 26.
Article
en En
| MEDLINE
| ID: mdl-35780959
ABSTRACT
NLRP3 inflammasome pathway-mediated inflammatory response is closely associated with depression. Increasing attention has been recently paid to the links between autophagy and depression, however, the relationship between autophagy and NLRP3 inflammasome in depressive behavior remain poorly understood. In the present study, the potential roles of autophagy-lysosome pathway in NLRP3 inflammasome regulation were investigated both in vivo (chronic unpredictable mild stress (CUMS)-induced depressive mouse model) and in vitro (LPS-induced cellular model) model. It demonstrated that CUMS induces depressive-like behaviors in mice, accompanied by increased expression of NLRP3 inflammasome and inflammatory responses. Meanwhile, it promoted the autophagosome marker LC3 and autophagic adapter protein p62 accumulation, accompanied by the decrease of lysosomal cathepsins B and D expression in the prefrontal cortex of mice. Notably, a significant colocalization of NLRP3 and LC3 in CUMS mice by immunofluorescence co-staining were observed. For the in vitro study, disrupting the lysosomal function with Baf A1 significantly increased the LPS-induced NLRP3 inflammasome accumulation and pro-inflammatory factors (IL-1ß and IL-18) production in BV2 cells. Collectively, our results suggested that the autophagic process is related to NLRP3 inflammasome activation, and dysfunctional lysosome in autophagy-lysosomal pathway may retard NLRP3 inflammasome degradation, facilitating the production of pro-inflammatory factors, thereby contributing to depressive behavior in CUMS mice.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inflamasomas
/
Proteína con Dominio Pirina 3 de la Familia NLR
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Behav Brain Res
Año:
2022
Tipo del documento:
Article
País de afiliación:
China