Decoding competitive endogenous RNA regulatory network in postoperative cognitive dysfunction

Abstract

Postoperative cognitive dysfunction (POCD) is a common postoperative neurological complication in elderly patients. Circular RNAs (circRNAs) are abundant in the mammalian brain and can probably regulate cognitive function. However, the competitive endogenous RNA (ceRNA) regulatory network in POCD remains illiterate. Transcriptomic signatures in the hippocampus of POCD mice derived from the Gene Expression Omnibus (GEO) dataset GSE190880, GSE95070, and GSE115440 were used to identify the circRNA, miRNA, and mRNA expression profiles of POCD mice compared with controls, respectively. A set of differentially expressed RNAs, including 119 circRNAs, 33 miRNAs, and 49 mRNAs were identified. Transcript validation showed the enhanced expression of circ_0001634, circ_0001345, and circ_0001493. A ceRNA regulatory network composed of three circRNAs, three miRNAs, and six mRNAs was established. The hub mRNAs in the ceRNA network were further found to be involved in the hormone catabolic process and regulation of canonical Wnt signaling pathway, revealing their crucial role in POCD. Finally, three miRNAs and four mRNAs were verified by qRT-PCR. These results based on bioinformatics and PCR array suggest that circ_0001634/miR-490-5p/Rbm47, circ_0001634/miR-490-5p/Sostdc1, circ_0001634/miR-7001-5p/Sostdc1, circ_0001345/miR-7001-5p/Sostdc1, and circ_0001493/miR-7001-5p/Sostdc1 may be novel diagnostic biomarkers and therapeutic targets for POCD.

Inhibition of PINK1-Mediated Mitophagy Contributes to Postoperative Cognitive Dysfunction through Activation of Caspase-3/GSDME-Dependent Pyroptosis

“…The open field test (OFT) was used to rule out the possibility that laparotomy-primed cognitive impairment arose from variations in spontaneous locomotor activity. 52 On the fourth day after surgery, the animals were placed in an open field apparatus (100 × 100 × 45 cm 3 ). The rats were individually placed in the center of the apparatus and allowed for 5 min free exploration.…”

“…Spatial learning and memory were assessed using the MWM test 5−10 d post laparotomy. 52 A 6 cm diameter hidden platform in the center of the fourth quadrant was submerged in a circular pool 160 cm in diameter and 50 cm in height. The MWM test comprised two phases: training four times per day for five consecutive days and probe trials without a platform on the sixth day.…”

“…Spatial learning and memory were assessed using the MWM test 5–10 d post laparotomy . A 6 cm diameter hidden platform in the center of the fourth quadrant was submerged in a circular pool 160 cm in diameter and 50 cm in height.…”

Construction and analysis of circular RNA-associated competing endogenous RNA network in the hippocampus of aged mice for the occurrence of postoperative cognitive dysfunction

“…Recent studies have shown that certain circRNAs were found to be aberrantly expressed in hippocampus, playing a role in POCD through ceRNA network ( Wu et al, 2021 ). A series of circRNAs were found to regulate hub genes such as Rbm47, Sostdc1, Egfr, Prkacb, Unc13c, Tbx20 and St8sia2 through ceRNA networks, participating in Wnt, P53 and NF-κB signaling pathways, associating with the development of POCD (At the Hop 50's Rock 'n' Roll, 1996; Cao et al, 2020 ; Wu et al, 2021 ; Wang et al, 2022 ). Although accumulating evidence explained the regulatory function of circRNAs in the brain, their roles in the perioperative context are still unknown area to be explored.…”