Ran Wei, Liang Ning, Yuan Ruixue, Wang Zhiqiao, Gao Jin
Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Front Mol Neurosci. 2022 Apr 14;15:836534. doi: 10.3389/fnmol.2022.836534. eCollection 2022.
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 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.
术后谵妄(POD)是老年患者常见的术后并发症,严重影响术后恢复。POD的确切机制仍不清楚。因此,有必要探讨POD在转录调控方面的机制。目前,环状RNA(circRNAs)已被证明在多种精神健康和认知障碍中发挥重要作用,如阿尔茨海默病、抑郁症和精神分裂症。为揭示circRNA对POD的影响,我们利用微阵列分析了12月龄小鼠胫骨骨折组和对照组海马中circRNAs的差异表达谱。共鉴定出14236个circRNAs。与对照组相比,表达增加的circRNAs有500个,表达减少的有187个。通过qRT-PCR进一步验证了微阵列数据的准确性。最后,基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路分析表明,轴突定向、泛素介导的蛋白水解、谷氨酸突触、雌激素信号通路、RAS信号通路等系统的变化可能是POD进展过程中的重要潜在病理机制。特别是,我们发现 基因及其转录本mmu_circRNA_26701在谷氨酸突触中特异性表达,这可能为这种难治性疾病的进展提供新的线索和干预靶点。