Transcriptomic Profiling in Aged Mice Reveals an Association Between Sevoflurane Anesthesia and Neurocognitive Dysfunction

TL;DR

This study finds that sevoflurane anesthesia in aged mice is linked to cognitive issues and changes in brain gene activity, especially in metabolism-related genes.

Contribution

The study identifies sevoflurane-induced transcriptomic changes in aged mice brains, specifically linking cognitive dysfunction to cysteine and methionine metabolism dysregulation.

Findings

Sevoflurane-exposed aged mice showed impaired spatial memory in the Morris water maze test.

Transcriptomic analysis revealed 148 differentially expressed genes linked to cysteine and methionine metabolism.

Altered gene expression suggests sevoflurane may suppress hippocampal function and disrupt metabolic pathways in aged mice.

Abstract

Sevoflurane is the most commonly used inhalational anesthetic in clinical work. Exposure to sevoflurane can induce cognitive dysfunction, particularly in the elderly. Transcriptomics aims to investigate diseases at the genetic level, identify enriched pathways and confirm action targets. This study investigates the mechanisms of sevoflurane-induced neurocognitive dysfunction in aged mice through transcriptomic analysis, aiming to establish a theoretical basis for the prevention and treatment of cognitive impairment. Eighteen-month-old aged mice were anesthetized with sevoflurane for 4 h. Hippocampal tissues were collected for transcriptomic analysis following the water maze test. Morris water maze (MWM) testing revealed that sevoflurane-exposed mice exhibited significantly longer escape latencies (b = 8.02, 95% CI [2.89, 13.16]) and fewer platform crossings (U = 65, Z = -2.018, P = 0.044) compared to controls. Transcriptomic profiling identified 148 differentially expressed genes (DEGs) associated with cysteine and methionine metabolism. KEGG enrichment analysis confirmed that the Cysteine and methionine metabolism pathway was the most significantly altered (FDR = 0.006). Sevoflurane may impair hippocampal function and our transcriptomic data suggest a potential association with dysregulation of metabolic pathways, particularly cysteine and methionine metabolism, which may contribute to cognitive impairment. Sevoflurane anesthesia is linked to transcriptomic alterations in the brains of aged mice, primarily affecting cysteine and methionine metabolism. Sevoflurane anesthesia may suppress widespread gene expression and could lead to the deactivation of functional networks in the brains of aged mice. The raw RNA-seq data have been deposited in the China National GeneBank Database (CNGBdb) under accession number CNP0007894.

The online version contains supplementary material available at 10.1007/s10571-026-01677-y.

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