This study aimed to investigate the role and underlying mechanism of lncRNA MIAT in sevoflurane (Sev)-induced cognitive dysfunction in neonatal rats, thereby offering theoretical basis for clinical intervention. Seven-day-old Sprague-Dawley (SD) rats were chosen to construct a Sev-induced cognitive dysfunction model. Anxiety-like behavior and locomotor activity were assessed by the open field test (OFT), whereas cognitive function was evaluated using novel object recognition (NOR) test and Morris water maze (MWM) test. The expression levels of lncRNA MIAT, miR-15b-5p, and Ccnd1 were detected by RT-qPCR. The dual-luciferase reporter gene assay was carried out to validate the targeted binding relationships. Sev exposure led to a downregulation of lncRNA MIAT expression in rat hippocampus. lncRNA MIAT alleviated Sev-induced cognitive impairment, as manifested by increased central zone residence time in OFT, elevated recognition index (RI) in NOR test, shortened escape latency, increased platform crossings, and prolonged target quadrant residence time in MWM test. Mechanistically, lncRNA MIAT directly targeted miR-15b-5p and inhibited its expression. miR-15b-5p targeted Ccnd1 and suppressed its expression. Overexpression of miR-15b-5p or silencing of Ccnd1 reversed the neuroprotective effect of lncRNA MIAT. LncRNA MIAT ameliorates Sev-induced cognitive dysfunction in neonatal rats by sponging miR-15b-5p to upregulate Ccnd1 expression, which may serve as a potential target for preventing Sev-related neurotoxicity.
Lu et al. (Mon,) studied this question.