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Sevoflurane induces cognitive dysfunction by modulating PER2 methylation to block AKT pathway-suppressed NLRP3

Shuangjiang Li1, Bin Wang1

  • 1Department of Anesthesiology, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, China.

Immunopharmacology and Immunotoxicology
|May 29, 2025
PubMed
Abstract

Insights

Sevoflurane anesthesia impairs cognitive function by altering DNA methylation in microglia. It suppresses Period2 (PER2) expression, activating inflammatory pathways and contributing to cognitive deficits.

Area of Science:

  • Neuroscience
  • Anesthesiology
  • Molecular Biology

Background:

  • Sevoflurane anesthesia is linked to cognitive dysfunction.
  • This dysfunction may involve DeoxyriboNucleic Acid (DNA) methylation processes.

Purpose of the Study:

  • To investigate the mechanism of sevoflurane-induced cognitive dysfunction.
  • To explore the role of DNA methylation and the Period2 (PER2) gene in this process.

Main Methods:

  • Utilized sevoflurane-induced rat models and microglial cell cultures.
  • Employed Morris water maze, Western blot, methylation analysis, immunofluorescence, and qRT-PCR.
  • Investigated the effects of PER2 overexpression and AKT inhibition (MK2206).

Main Results:

  • Sevoflurane induced cognitive deficits, increased inflammatory markers (NLRP3, IL-18, IL-1β, Iba-1), and decreased PER2 expression via methylation.
  • PER2 was localized in microglia, and its suppression by sevoflurane was confirmed in vitro.
  • PER2 overexpression counteracted sevoflurane's effects on inflammation and AKT activation, while MK2206 reversed these findings.

Conclusions:

  • Sevoflurane contributes to cognitive dysfunction by modulating PER2 methylation in microglia.
  • This modulation impacts the AKT pathway and NLRP3 inflammasomes, leading to impaired cognition.
Keywords:
AKTNLRP3PER2cognitive dysfunctioninflammasomessevoflurane

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