Abstract
Circular RNA (circRNA) has been well studied in many diseases, whereas their role in patients with postoperative cognitive dysfunction (POCD) remains largely unclear. Here, we investigated the therapeutic effects of dexmedetomidine (Dex) on POCD and analyzed the role of circRNA as well as the pathways that may be involved. The Morris water maze test demonstrated that POCD rats have a longer incubation period than the normal group, but the latency of POCD rats was significantly lower after Dex treatment. Moreover, HE staining showed that Dex improved hippocampal pathological changes. RNA sequencing showed 164 differentially expressed circRNAs between POCD and Dex groups; 74 were upregulated and 90 were downregulated in the Dex group. A total of 20,790 target genes for differentially expressed circRNAs were observed in RNAhybrid and Miranda databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the target genes of differentially expressed circRNAs are mainly focused on positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage, negative regulation of cell adhesion mediated by integrin, and response to cytokines and other function of life activities and involved in the P53 signaling pathway and nuclear factor kappa B (NF-κB) signaling pathway. Furthermore, the expression of five candidate circRNAs (circ-Shank3, circ-Cdc42bpa, circ-chrx-24658, cir-chr17-3642 and circ-Sgsm1) and target genes were consistent with the RNA sequencing results, which was verified by quantitative real-time polymerase chain reaction (qRT-PCR). These results indicate that circ-Shank3 participate in the process of Dex improved POCD through regulating the P53 and NF-κB signaling pathways and may potentially facilitate POCD treatment through the development of clinical drugs.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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YH contributed to conceptualization and funding acquisition: YH. Data curation: CC and FD. CC and FD were involved in formal analysis. CC and FD were involved in investigation. CC and FD were involved in methodology.CC and FD contributed to writing—original draft. CC and FD contributed to writing— review and editing. All the authors read and approved the final manuscript.
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This study was approved by the Institutional Animal Care and Use Committee of the Second Affiliated Hospital of Nanchang University. All animal experiments were performed in accordance with the Guides for the Care and Use of Laboratory Animals.
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Supplementary file1 Figure S1. The expression pattern of circRNAs was examined by RNA sequencing during the Dex treatment of POCD rats. The results showed that the higher the number of exons covered, the fewer the circRNAs. (A) The statistical chart of exon number count covered by circRNAs. (B) The number of circRNAs distributed on each chromosome number. Among them, the number of circRNAs on chromosomes 1, 2, and 6 were all greater than 500.
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Cao, C., Deng, F. & Hu, Y. Dexmedetomidine alleviates postoperative cognitive dysfunction through circular RNA in aged rats. 3 Biotech 10, 176 (2020). https://doi.org/10.1007/s13205-020-2163-0
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DOI: https://doi.org/10.1007/s13205-020-2163-0