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Updated: Jul 1, 2025
A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration
Published on: February 27, 2018
CircAKT3 alleviates postoperative cognitive dysfunction by stabilizing the feedback cycle of miR-106a-5p/HDAC4/MEF2C
Xuan Wang1, Xiaole Tang2, Pengfei Zhu1
1Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.
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.
Insights
Circular RNAs (circRNAs) show promise for treating postoperative cognitive dysfunction (POCD). This study found circAKT3 alleviates POCD by reducing neuronal apoptosis and modulating miRNA and protein levels.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are gaining attention for their role in neurodegenerative diseases.
- The involvement of circRNAs in postoperative cognitive dysfunction (POCD) remains largely uncharacterized.
Purpose of the Study:
- To investigate the role of circRNAs in POCD.
- To identify specific circRNAs and their molecular mechanisms involved in POCD pathogenesis.
Main Methods:
- Whole transcriptome sequencing was performed to identify differentially expressed genes in POCD mouse models.
- Bioinformatics analysis was used to elucidate molecular interactions.
- In vitro and in vivo experiments were conducted to validate findings.
Main Results:
- circAKT3 was identified and found to be associated with hippocampal neuronal apoptosis in POCD mice.
- Overexpression of circAKT3 reduced hippocampal neuronal apoptosis and alleviated POCD.
- circAKT3 modulated the miR-106a-5p/HDAC4/MEF2C pathway, forming a positive feedback loop.
Conclusions:
- circAKT3 plays a protective role in POCD by inhibiting neuronal apoptosis.
- The circAKT3/miR-106a-5p/HDAC4/MEF2C axis represents a potential therapeutic target for POCD.
- This study reveals novel circRNA-miRNA-mRNA regulatory pathways relevant to POCD.
