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MicroRNA-669f-5p targeting deoxycytidinephosphate deaminase contributes to sevoflurane-induced cognitive impairments in aged mice via the TLR2/4–MyD88–NF-κB pathway

Year: 2025

Type: article

Abstract: Postoperative cognitive dysfunction (POCD) is a common complication associated with sevoflurane anaesthesia in the aged population. MicroRNAs have been implicated in sevoflurane-induced cognitive deficits; however, the role and underlying mechanism of microRNA (miR)-669f-5p remain unclear. Eighteen-month-old mice and mouse hippocampal neurons (HT22) were exposed to sevoflurane. Cognitive function was assessed using the Morris water maze test. Neuroapoptosis and cellular proliferation were evaluated by terminal-deoxynucleotidyl transferase-mediated nick end-labelling staining and Cell Counting Kit-8 assays, respectively. The downstream molecular mechanisms of miR-669f-5p were investigated using bioinformatics analysis, western blotting, quantitative real-time polymerase chain reaction, immunofluorescence and dual-luciferase reporter assays. Bioinformatics analysis of the Gene Expression Omnibus database revealed upregulation of miR-669f-5p in hippocampal tissue from mice with POCD. Inhibition of miR-669f-5p substantially improved sevoflurane-induced cognitive impairment in aged mice. Deoxycytidinephosphate deaminase (Dctd) was identified as a direct target of miR-669f-5p. Overexpression of Dctd reversed the effects of miR-669f-5p mimics on apoptosis and proliferation in HT22 cells and suppressed activation of the TLR2/4–MyD88–NF-κB signalling pathway. Moreover, Dctd overexpression ameliorated sevoflurane-induced cognitive impairment in aged mice. MicroRNA-669f-5p contributes to sevoflurane-induced cognitive impairment in aged mice by targeting Dctd and activating the TLR2/4–MyD88–NF-κB pathway. These findings provide new insights into potential therapeutic strategies for anaesthesia-related POCD. • MiR-669f-5p expression was found to be up-regulated in the hippocampus of POCD patients, and inhibition of miR-669f-5p significantly improved cognitive impairment induced by sevoflurane in aged mice. • Molecular mechanisms, miR-669f-5p could contribute significantly to sevoflurane-induced cognitive impairment in aged mice by targeting Dcdt and via TLR2/4-MyD88-NF-κB signaling pathway. • This study provides an in-depth understanding of the mechanisms underlying sevoflurane-induced cognitive impairment and provides new perspectives and potential strategies for the prevention and treatment of POCD in elderly patients.

Source: Brain Research Bulletin

DOI: 10.1016/j.brainresbull.2025.111381