Sevoflurane Augments Neuroinflammation by Regulating DUSP6 Via YTHDF1 in Postoperative Cognitive Dysfunction

Overview

Journal Toxicol Res (Camb)

Publisher Oxford University Press

Date 2024 Jul 5

PMID 38966092

Authors

Jie Ding

Kai Zhang

Dongwei Wang

Qingdong Wang

Affiliations

Soon will be listed here.

Abstract

Background: Postoperative cognitive dysfunction (POCD) is a generally recognized complication experienced by patients who receive anesthesia during surgery. Sevoflurane, the most commonly used inhaled anesthetic, has been shown to trigger neuroinflammation that promotes to POCD.

Objective: This study examined the pathological mechanism by which sevoflurane causes neuroinflammation, participating in POCD.

Methods: To establish a neurocyte injury model, the human neuroblastoma cell lines SH-SY5Y and SK-N-SH were treated with sevoflurane. Cell viability was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assays. The reactive oxygen species (ROS) level was evaluated by DCFH-DA assays. A lactate dehydrogenase (LDH) Cytotoxicity Assay Kit was used to measure LDH levels. Inflammatory cytokine levels were measured using enzyme-linked immunosorbent assay assays. Gene expression densities and protein abundance were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) or western blotting. The interaction between YTHDF1 and dual specific phosphatase 6 (DUSP6) was validated using RNA immunoprecipitation (RIP)-qPCR and methylated RIP (MeRIP)-qPCR assays. Flow cytometry was performed to determine apoptosis.

Results: Sevoflurane promoted apoptosis, oxidative stress, and neuroinflammation and repressed the expression levels of YTHDF1 and DUSP6. Furthermore, YTHDF1 overexpression reversed sevoflurane-induced neuroinflammation in neurocytes. DUSP6 overexpression could alleviate the neuroinflammation induced by sevoflurane via regulating the extracellular signal-regulated kinase (ERK)1/2 signaling pathway. Moreover, YTHDF1 enhanced DUSP6 expression.

Conclusion: Sevoflurane-stimulated neuroinflammation by regulating DUSP6 via YTHDF1. Sevoflurane promoted neuroinflammation by regulating DUSP6 via YTHDF1 in an in vitro model of POCD.

Citing Articles

Downregulation of circTLK1 improves the impairments in learning and memory induced by anesthetics via regulating miR-374b-5p expression and reducing neuroinflammation.

Zhu X Toxicol Res (Camb). 2024; 13(6):tfae220.

PMID: 39712639 PMC: 11659641. DOI: 10.1093/toxres/tfae220.

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