Akkermansia muciniphila-derived small extracellular vesicles attenuate intestinal ischemia-reperfusion-induced postoperative cognitive dysfunction by suppressing microglia activation via the TLR2/4 signaling.
Biochim Biophys Acta Mol Cell Res
; 1871(2): 119630, 2024 02.
Article
em En
| MEDLINE
| ID: mdl-37967793
ABSTRACT
Akkermansia muciniphila (AKK) bacteria improve the functions of theere intestinal and blood-brain barriers (BBB) via their extracellular vesicles (AmEvs). However, their role in postoperative cognitive dysfunction (POCD) and its underlying mechanisms remain unclear. To investigate, we used C57BL/6â¯J mice divided into five groups Sham, POCD, POCD+Akk, POCD+Evs, and POCD+Evsâ¯+â¯PLX5622. POCD was induced through intestinal ischemia-reperfusion (I/R). The mice's cognitive function was assessed using behavioral tests, and possible mechanisms were explored by examining gut and BBB permeability, inflammation, and microglial function. Toll-like receptor (TLR) 2/4 pathway-related proteins were also investigated both in vitro and in vivo. PLX5622 chow was employed to eliminate microglial cells. Our findings revealed a negative correlation between AKK abundance and POCD symptoms. Supplementation with either AKK or AmEvs improved cognitive function, improved the performance of the intestinal barrier and BBB, and decreased inflammation and microglial activation in POCD mice compared to controls. Moreover, AmEvs treatment inhibited TLR2/4 signaling in the brains of POCD mice and LPS-treated microglial cells. In microglial-ablated POCD mice, however, AmEvs failed to protect BBB integrity. Overall, AmEvs is a potential therapeutic strategy for managing POCD by enhancing gut and BBB integrity and inhibiting microglial-mediated TLR2/4 signaling.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Orgânicos
/
Vesículas Extracelulares
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Complicações Cognitivas Pós-Operatórias
Limite:
Animals
Idioma:
En
Revista:
Biochim Biophys Acta Mol Cell Res
Ano de publicação:
2024
Tipo de documento:
Article