MicroRNA-669f-5p targeting deoxycytidinephosphate deaminase contributes to sevoflurane-induced cognitive impairments in aged mice via the TLR2/4–MyD88–NF-κB pathway
Background: 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 unclea...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-08-01
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| Series: | Brain Research Bulletin |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025001935 |
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| Summary: | Background: 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. Methods: 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. Results: 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. Conclusion: 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. |
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| ISSN: | 1873-2747 |