Dataset Information

CircAKT3 alleviates postoperative cognitive dysfunction by stabilizing the feedback cycle of miR-106a-5p/HDAC4/MEF2C axis in hippocampi of aged mice.

ABSTRACT: Circular RNAs (circRNAs) have garnered significant attention in the field of neurodegenerative diseases including Alzheimer's diseases due to their covalently closed loop structure. However, the involvement of circRNAs in postoperative cognitive dysfunction (POCD) is still largely unexplored. To identify the genes differentially expressed between non-POCD (NPOCD) and POCD mice, we conducted the whole transcriptome sequencing initially in this study. According to the expression profiles, we observed that circAKT3 was associated with hippocampal neuronal apoptosis in POCD mice. Moreover, we found that circAKT3 overexpression reduced apoptosis of hippocampal neurons and alleviated POCD. Subsequently, through bioinformatics analysis, our data showed that circAKT3 overexpression in vitro and in vivo elevated the abundance of miR-106a-5p significantly, resulting in a decrease of HDAC4 protein and an increase of MEF2C protein. Additionally, this effect of circAKT3 was blocked by miR-106a-5p inhibitor. Interestingly, MEF2C could activate the transcription of miR-106a-5p promoter and form a positive feedback loop. Therefore, our findings revealed more potential modulation ways between circRNA-miRNA and miRNA-mRNA, providing different directions and targets for preclinical studies of POCD.

SUBMITTER: Wang X

PROVIDER: S-EPMC10937803 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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CircAKT3 alleviates postoperative cognitive dysfunction by stabilizing the feedback cycle of miR-106a-5p/HDAC4/MEF2C axis in hippocampi of aged mice.

Wang Xuan X Tang Xiaole X Zhu Pengfei P Hua Dongyu D Xie Zheng Z Guo Mingke M Que Mengxin M Yan Jing J Li Xing X Xia Qian Q Luo Xiaoxiao X Bi Jiangjiang J Zhao Yilin Y Zhou Zhiqiang Z Li Shiyong S Luo Ailin A

Cellular and molecular life sciences : CMLS 20240313 1

Circular RNAs (circRNAs) have garnered significant attention in the field of neurodegenerative diseases including Alzheimer's diseases due to their covalently closed loop structure. However, the involvement of circRNAs in postoperative cognitive dysfunction (POCD) is still largely unexplored. To identify the genes differentially expressed between non-POCD (NPOCD) and POCD mice, we conducted the whole transcriptome sequencing initially in this study. According to the expression profiles, we obser ...[more]

PMID: 38478029

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Project description:BackgroundMethamphetamine (METH) is a highly addictive, psychoactive drug which can harm individual health and lead to great social problems. Various approaches have been adopted to address the problems arising from METH addiction, but relapse rates remain high. Recently, it has been found that comprehensive treatment combined with scientific and appropriate exercise interventions can improve the mental state and physical fitness of drug addicts and promote their physical and mental rehabilitation. Long-term, regular exercise improves the symptoms of METH withdrawal and reduces METH relapse. This study aimed to investigate the effects and regulated gene expression related to running exercise in METH-addicted mice.MethodsMale C57BL/6J mice were used to construct a METH addiction model. We performed a running exercise intervention and used conditioned place preference (CPP) to measure the effects of the running intervention on the METH-addicted mice. We also performed RNA sequencing (RNA-seq) and transcriptome analysis on the mice hippocampi, and the functions and differentially expressed genes (DEGs) that were significantly regulated by exercise intervention in the METH-addicted mice were analyzed and noted.ResultsThe results showed that days of CPP were shortened to 3 days in METH-addicted mice that underwent moderate exercise intervention, compared to 6 days in METH-addicted mice that went without exercise intervention. In addition, hippocampal transcriptome analysis revealed 12 DEGs significantly regulated by exercise intervention. By performing Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, it was revealed that the function of immune responses was significantly enriched in the METH-addicted mice undertaking exercise. The expression of 12 DEGs was verified by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), which showed that relative messenger RNA (mRNA) expression of DEGs was consistent with the RNA-seq results.ConclusionsA running intervention can promote the recovery of METH addiction in mice, and the 12 candidate DEGs from the mouse hippocampus can be used for further research on the regulatory mechanisms of exercise in METH-addicted mice.

Dataset Information

CircAKT3 alleviates postoperative cognitive dysfunction by stabilizing the feedback cycle of miR-106a-5p/HDAC4/MEF2C axis in hippocampi of aged mice.

Publications

CircAKT3 alleviates postoperative cognitive dysfunction by stabilizing the feedback cycle of miR-106a-5p/HDAC4/MEF2C axis in hippocampi of aged mice.

Similar Datasets

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