Depletion of PIEZO1 expression is accompanied by upregulating p53 signaling in mice with perioperative neurocognitive disorder

Abstract

Abstract As the common complications observed in surgical elder patients, perioperative neurocognitive disorders (PND) cause a series of serious perioperative health problems. However, there are no effective treatments, and the exact mechanisms are still largely unknown. In this study, transcriptome sequencing was performed to investigate the differentially expressed genes (DEGs)in the hippocampus of C57BL/6J aged mice with or without PND. Compared with the Mock group, the expression of 352, 395, and 772 genes changed significantly in the PND group at day 1, 7, and 21 after surgery, respectively. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) showed that DEGs were mainly associated with p53 signaling. Moreover, GSEA revealed that potentially p53-related DEGs such as leucine-rich repeat serine/threonine-protein kinase 1 (LRRK1), monooxygenase DBH-like 1 (MOXD1), and piezo type mechanosensitive ion channel component 1 (PIEZO1). Furthermore, we confirmed the decreased interaction of PIEZO1 with p53 in PND, and upregulation of PIEZO1 resulted in a decrease in p53 protein levels through increased ubiquitination of p53. In conclusion, this study contributes to the knowledge of global changes in gene expression and mechanisms during PND.