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Journal Article Epublish 3 citations

PubMed: 39707048 DOI: 10.1007/s10565-024-09964-4

Mechanistic insights into sevoflurane-induced hippocampal neuronal damage and cognitive dysfunction through the NEAT1/Nrf2 signaling axis in aged rats.

Cell Biol Toxicol 41(1):13

Authors: Yiliang Wang, Nu Li, Xiaoyu Chen, Yue Zhao, Letian Qu, Dasheng Cai

Affiliations

  • Department of Anesthesiology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, People's Republic of China. Department of Health Statistics, School of Public Health, China Medical University, Shenyang, 110122, Liaoning, People's Republic of China.
  • Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, People's Republic of China.
  • Department of Anesthesiology, General Hospital of Northern Theater Command, Shenyang, 110001, Liaoning, People's Republic of China.
  • Department of Anesthesiology, Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, 110001, Liaoning, People's Republic of China.
  • Department of Geriatrics, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, People's Republic of China.
  • Department of Anesthesiology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, People's Republic of China.

Abstract

The use of anesthetics during surgery can cause severe neurological damage and cognitive dysfunction in elderly patients. However, this health issue currently lacks corresponding therapeutic strategies. This research involved the utilization of single-cell RNA sequencing (scRNA-seq) and transcriptomic assessment to pinpoint crucial cell classifications and molecular pathways, as well as the lncRNA expression profiles, that undergo substantial alterations in aged rats experiencing sevoflurane-induced cognitive impairment. The results of our investigation pointed towards the enrichment of differentially expressed genes in neurons within the Nrf2/ARE signaling pathway, alongside an elevated expression of lncRNA NEAT1. Subsequently, by constructing a rat model to induce neuronal dysfunction with sevoflurane and performing experiments both in vivo and in vitro (including TUNEL staining, H&E staining, immunohistochemistry, immunofluorescence, and flow cytometry to assess apoptosis levels), we confirmed that NEAT1 inhibits the Nrf2/ARE/HO-1 pathway-related factors. Sevoflurane promotes oxidative stress and apoptosis in primary hippocampal neurons through the NEAT1/Nrf2/ARE/HO-1 axis. This study elucidates the molecular mechanism by which sevoflurane induces hippocampal neuronal damage and cognitive decline in elderly rats via the regulation of the lncRNA NEAT1/Nrf2 signaling axis. We discovered that upregulation of NEAT1 suppresses the Nrf2 signaling pathway, further inducing neuronal damage and cognitive dysfunction, furnishing an essential citation to grasp the molecular pathways involved in neuronal harm and devising corresponding treatment methodologies.

MeSH

Cells, Sevoflurane, Neurons, Cognitive Dysfunction, Aged, Cell Biology, Toxicology, Therapeutics, Apoptosis