MiR-214-3p Prevents the Development of Perioperative Neurocognitive Disorders in Elderly Rats

Objective:This study aimed to identify microRNAs(miRNAs)involved in the development of perioperative neurocognitive disorders(PND).Methods:Plasma exosomal miRNA expression was examined in patients before and after cardiopulmonary bypass(CPB)using microarray and qRT-PCR and these patients were diagnosed as PND later.Elderly rats were subjected to CPB,and the cognitive functions were examined.Bioinformatics analysis was conducted to predict the targets of miR-214-3p.Rats were administered rno-miR-214-3p agomir before or after CPB to investigate the role of miR-214-3p in PND development.Results:We identified 76 differentially expressed plasma exosomal miRNAs in PND patients after surgery(P<0.05,|log2FC|>0.58),including the upregulated hsa-miR-214-3p(P=0.002399392).Prostaglandin-endoperoxide synthase 2(PTGS2)was predicted as a miR-214-3p target.In rats,CPB reduced the platform crossing numbers and target quadrant stay time,accompanied with hippocampal neuronal necrosis.The rno-miR-214-3p level was significantly increased in plasma exosomes but decreased in rat hippocampus after surgery,exhibiting a negative correlation(P<0.001,r=-0.762).A negative correlation between miR-214-3p and PTGS2 protein expression was also observed in the hippocampus after surgery.Importantly,rno-miR-214-3p agomir treatment,before or after surgery,significantly increased the platform crossing numbers(P=0.035)and target quadrant stay time(P=0.029)compared with negative control.Hippocampal PTGS2 protein level was increased in the untreated surgery group and decreased in response to rno-miR-214-3p agomir treatment before or after surgery(both P<0.05 vs.negative control).Conclusion:These data suggest that miR-214-3p/PTGS2 signaling contributes to the development of PND,serving as a potential therapeutic target for PND.