NLRP3 activation in microglia contributes to learning and memory impairment induced by chronic lead exposure in mice.
Toxicol Sci
; 191(1): 179-191, 2023 01 31.
Article
em En
| MEDLINE
| ID: mdl-36308466
ABSTRACT
Lead (Pb)-induced microglial activation and neuroinflammation has been considered as one of the main pathological events of Pb neurotoxicity. The NLRP3 inflammasome signaling pathway is a major contributor to the neuroinflammatory process in the central nervous system. However, the relationship between chronic Pb exposure and neurogenic NLRP3 inflammasome is unclear. Therefore, the aim of this study was to characterize the role of NLRP3 inflammasome activation during the chronic Pb exposure using in vitro and in vivo models. Our results showed that chronic Pb exposure induce learning and memory impairment in mice, mainly related to the activation of microglia and NLRP3 inflammasome. This phenomenon was reversed in mice by treating with the NLRP3 inhibitor MCC950 and using NLRP3-/- mice. In addition, Pb caused the activation of NLRP3 inflammasome, the production of mitochondrial ROS (mtROS), and mitochondrial Ca2+ overload in BV2 cells. Amelioration of mtROS abolished Pb-induced NLRP3 inflammasome activation. Moreover, after regulation of Ca2+ redistribution, mtROS and NLRP3 inflammasome activation was restored. In conclusion, NLRP3 inflammasome activation in microglia plays a vital role in Pb neurotoxicity, by a novel mechanism of enhancing mtROS production and Ca2+ redistribution.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inflamassomos
/
Proteína 3 que Contém Domínio de Pirina da Família NLR
Limite:
Animals
Idioma:
En
Revista:
Toxicol Sci
Assunto da revista:
TOXICOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China