Identification of Potential Key circRNAs in Aged Mice With Postoperative Delirium

Abstract

Postoperative delirium (POD) is a common postoperative complication in elderly patients and seriously affects postoperative recovery. The exact mechanism of POD is still unclear. Therefore, it is necessary to explore the mechanism of POD in transcriptional regulation. At present, circRNAs have been proven to play an important role in a variety of mental health and cognitive disorders, such as Alzheimer’s disease, depression and schizophrenia. To reveal the effect of circRNA on POD, we used microarray to analyze the differential expression profiles of circRNAs in the hippocampus of 12-month-old mice between the tibial fracture and control groups. A total of 1,4236 circRNAs were identified. Compared with the control group, there were 500 circRNAs with increased expression and 187 with decreased expression. The accuracy of the microarray data was further verified by qRT–PCR. Finally, GO enrichment and KEGG pathway analyses indicated that changes in axon orientation, ubiquitin-mediated proteolysis, glutamate synapses, the estrogen signaling pathway, the RAS signaling pathway and other systems may be important potential pathological mechanisms in the progression of POD. In particular, we found that the HOMER1 gene and its transcript mmu_circRNA_26701 are specifically expressed in the glutamate synapse, which may provide new clues and intervention targets for the progression of this refractory disease.

Recent progress on the role of non-coding RNA in postoperative cognitive dysfunction

“…According to the latest consensus ( Evered et al, 2018b ), the term of “perioperative neurocognitive dysfunction (PND),” further classified into postoperative delirium (POD, the early stage of postoperative cognitive changes occurred up to seven days after surgery) and POCD (the late stage of postoperative cognitive changes diagnosed thereafter until 12 months), is recommended to describe the overall cognitive function demonstrated during the perioperative periods. Evidence for the role of ncRNAs in POD has increased in the past few years ( Ran et al, 2022 ; Wang et al, 2022a ). However, in two different microarray studies, performed to identify differentially expressed lncRNAs and mRNAs in POD and POCD, no overlap was observed between POD and POCD patients ( Zhang et al, 2018 ; Song et al, 2021 ).…”

Comprehensive analysis of dysregulated circular RNAs and construction of a ceRNA network involved in the pathology of Alzheimer’s disease in a 5 × FAD mouse model

“…circRNA00825 and circRNA01985 were aberrantly upregulated in the brain of APP/PS1 mice ( Ma et al, 2019 ; Wei et al, 2022 ). In aged C57BL/6J mice, circRNA03073 and circRNA08440 were found to have aberrant downregulation in the hippocampus of mice ( Ran et al, 2022 ). However, the abnormal circRNAs found in the brains of SAMP8 mice and Tg2576 transgenic AD mice are different from those in the hippocampus of 5 × FAD mice in our study( Lee et al, 2019 ; Zhang Y. et al, 2021 ).…”

Decoding competitive endogenous RNA regulatory network in postoperative cognitive dysfunction

“…The circRNA dataset (GSE190880) was retrieved from the GPL21826 platform and contained 3 pairs of hippocampus from POCD and control mice ( Ran et al, 2022 ). The miRNA dataset (GSE95070) was retrieved from the GPL19117 platform and contained 5 pairs of hippocampus from POCD and control mice ( Wei et al, 2017 ).…”