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

Area of Science:

• Neuroscience
• Molecular Biology
• Biomarkers

Background:

• Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients after anesthesia.
• The underlying mechanisms of POCD, particularly the role of microRNAs, remain incompletely understood.

Purpose of the Study:

• To investigate the role of miR-371a-3p in POCD.
• To explore the potential of miR-371a-3p as a predictive biomarker for POCD.
• To elucidate the molecular mechanisms by which miR-371a-3p influences cognitive function.

Main Methods:

• Analysis of miR-371a-3p expression in 143 elderly orthopedic patients categorized into POCD and non-POCD groups.
• Assessment of miR-371a-3p's predictive value using MoCA scores.
• In vivo studies using sevoflurane-induced cognitive dysfunction in rats (MWM test).
• In vitro studies on sevoflurane-exposed HT22 cells to examine miR-371a-3p's effects on cell viability, apoptosis, inflammation, oxidative stress, and ferroptosis.
• Validation of miR-371a-3p targeting FKBP5 using bioinformatics and dual-luciferase assays.

Main Results:

• miR-371a-3p was significantly downregulated in POCD patients and showed predictive efficacy.
• Administration of agomir-371a-3p improved cognitive function in sevoflurane-treated rats.
• Overexpression of miR-371a-3p in vitro mitigated sevoflurane-induced neuronal damage, including reduced apoptosis, inflammation, oxidative stress, and ferroptosis.
• miR-371a-3p directly targets and regulates FKBP5, and FKBP5 overexpression reversed the protective effects of miR-371a-3p.

Conclusions:

• miR-371a-3p serves as a potential predictive biomarker for POCD.
• miR-371a-3p ameliorates sevoflurane-induced cognitive dysfunction in rats.
• Upregulating miR-371a-3p, potentially by targeting FKBP5, offers a novel therapeutic avenue for POCD.