miR‐371a‐3p Overexpression Alleviates Cognitive Dysfunction Via Targeted Negative Regulation of FKBP5

The study aims to explore the role of miR-371a-3p in cognitive dysfunction and its underlying mechanisms. This research comprised 143 elderly orthopedic patients undergoing anesthesia. They were further categorized into POCD and NPOCD groups based on postoperative MoCA scores. The relative expression and predictive value of miR-371a-3p in POCD were analyzed. The effects of miR-371a-3p on cognitive dysfunction in rats were assessed by the MWM test. The impact of miR-371a-3p overexpression on cell viability, apoptosis, apoptosis-related genes, inflammatory response, oxidative stress, and ferroptosis-related factors was examined in sev-induced HT22 cells. The target relationship between miR-371a-3p and FKBP5 was validated via database and dual luciferase assays. miR-371a-3p was markedly downregulated in POCD patients. miR-371a-3p demonstrated good predictive efficacy for POCD. Agomir-371a-3p effectively shortened the escape latency period, prolonged the dwell time in the target quadrant, and increased the platform crossing frequency in sev-induced rats. Concurrently, low miR-371a-3p expression was discovered in rat hippocampal tissue and HT22 cells exposed to sev. miR-371a-3p overexpression mitigates the decrease in cell vitality and increased apoptosis in sev-induced HT22 cells, and improves the inflammatory response, oxidative stress, and ferroptosis. Mechanistically, miR-371a-3p targets and regulates FKBP5. FKBP5 overexpression reverses the effects of miR-371a-3p on sev-induced neuronal cell damage. miR-371a-3p is a promising predictive biomarker for POCD. Agomir-371a-3p ameliorates sev-induced cognitive dysfunction in rats. Overexpression of miR-371a-3p alleviates sev-induced cognitive dysfunction by targeting FKBP5, offering a novel therapeutic approach for POCD.