Brain research bulletin
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Brain research bulletin · Jul 2021
NLRP3 inflammasome inhibition by histone acetylation ameliorates sevoflurane-induced cognitive impairment in aged mice by activating the autophagy pathway.
Age-related cognitive impairment is associated with diminished autophagy and progressively increased neuroinflammation. Histone acetylation has been shown to be a key process in sevoflurane-induced neurobehavioral abnormalities. Here, we investigated whether histone acetylation regulates the interaction between autophagy and the NLRP3 inflammasome in models of sevoflurane-induced cognitive impairment and explored the underlying molecular mechanisms. ⋯ Cognitive deficits and inadequate autophagy induced by sevoflurane were reversed and NLRP3 inflammasome activation was inhibited by SAHA. Treatment with 3-MA, an autophagy inhibitor, eliminated the neuroprotective effects of SAHA on improving cognition in mice, activating autophagy and downregulating the NLRP3 inflammasome. Based on these results, histone acetylation activates autophagy plays an important role in inhibiting the activation of the NLRP3 inflammasome to protect the host from excessive neuroinflammation and sevoflurane-induced cognitive dysfunction in the aging brain.