Sevoflurane inhibits histone acetylation and contributes to cognitive dysfunction by enhancing the expression of ANP32A in aging mice

Sevoflurane inhibits histone acetylation and contributes to cognitive dysfunction by enhancing the expression of ANP32A in aging mice

Postoperative cognitive dysfunction (POCD) is a major clinical complication after surgery under general anesthesia, particularly in elderly patients, but the mechanisms remain unclear. We recently found that the anaesthetization of aging C57BL/6 J mice (14–16 months) with sevoflurane (3%, two hours...

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Bibliographic Details
Published in:Behavioural brain research Vol. 431; p. 113949
Main Authors: Chai, Gaoshang, Wu, Jiajun, Fang, Rongfei, Liu, Yanlin, Wang, Xuechun, Wang, Xi, Zhang, Jinming, Zhou, Jiali, Jiang, Zhiqian, Yi, Haiyan, Nie, Yunjuan, Zhao, Peng, Zhang, Dengxin
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 05-08-2022
Subjects:
ANP32A
Cognitive dysfunction
Histone acetylation
POCD
Sevoflurane
C/EBPβ
MWM
AD
HDACs
ANP32A
POCD
fEPSPs
LTP
Histone acetylation
SYP
SYN1
Sevoflurane
htau
HFS
aCSF
HATs
GluN2A
GluN2B
Cognitive dysfunction
INHAT
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Summary:Postoperative cognitive dysfunction (POCD) is a major clinical complication after surgery under general anesthesia, particularly in elderly patients, but the mechanisms remain unclear. We recently found that the anaesthetization of aging C57BL/6 J mice (14–16 months) with sevoflurane (3%, two hours each day for three consecutive days) can induce cognitive dysfunction and synaptic plasticity deficits. Further studies demonstrated that sevoflurane induced ANP32A (acidic leucine-rich nuclear phosphoprotein-32A) overexpression by stimulating C/EBPβ (CCAAT/enhancer binding protein-β), which could suppress histone acetylation at H3K18, H3K14, H4K5, and H4K12 and decrease the binding of H3K18 and H3K14 to the promoters of GluN2B and GluN2A, respectively. These results suggest that sevoflurane can inhibit histone acetylation and contribute to cognitive dysfunction by enhancing the expression of ANP32A in aging mice. Our study provides new insights into aging-associated POCD and potential molecular markers for protection. •Sevoflurane impairs synaptic plasticity and cognitive function in aged mice.•Sevoflurane inhibits histone acetylation at H3K18, H3K14, H4K5, and H4K12.•Sevoflurane decreased binding of H3K18 to the promoter of GluN2B and H3K14 to the promoter of GluN2A gene.•Sevoflurane increased ANP32A expression by activating C/EBPβ.
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ISSN:0166-4328
1872-7549
DOI:10.1016/j.bbr.2022.113949