Role of the circRNA_34414/miR‐6960a‐5p/SIRT3 axis in postoperative delirium via CA1 Vglut1+ neurons in older mice

Abstract

AbstractAimsPostoperative delirium (POD) is a common neurological complication in elderly patients after anesthesia/surgery. The main purpose of this study is to explore the effect of circRNA‐targeted miRNA regulating SIRT3 on mitochondrial function through ceRNA mechanism under the surgical model of tibial fracture and to further explore the potential mechanism of postoperative delirium mediated by circRNA, so as to provide new ideas for clinical diagnosis and prevention of POD.MethodsThe surgical model of tibial fracture under sevoflurane anesthesia caused acute delirium‐like behavior in elderly mice. We observed that the decrease of SIRT3 and mitochondrial dysfunction was related to POD, and miRNA and circRNA (circRNA_34414) related to SIRT3 were further studied. Through luciferase and RAP, we observed that circRNA_34414, as a miRNA sponge, was involved in the regulation of SIRT3 expression.ResultsPostoperative delirium in elderly mice showed decreased expression of hippocampal circRNA_34414, increased expression of miR‐6960‐5p, decreased expression of SIRT3, and impaired mitochondrial membrane potential. Overexpression of circRNA_34414, or knockdown of miR‐6960‐5p, or overexpression of SIRT3 in hippocampal CA1 glutamatergic neurons significantly upregulated hippocampal SIRT3 expression, increased mitochondrial membrane potential levels, and significantly ameliorated postoperative delirium in aged mice; CircRNA_34414 ameliorates postoperative delirium in mice, possibly by targeting miR‐6960‐5p to upregulate SIRT3.ConclusionsCircRNA_34414 is involved in the improvement of postoperative delirium induced by anesthesia/surgery by upregulating SIRT3 via sponging miR‐6960‐5p.