Related Experiment Video
Updated: May 5, 2026
Stereotactic Injection of MicroRNA-expressing Lentiviruses to the Mouse Hippocampus CA1 Region and Assessment of the Behavioral Outcome
Published on: June 10, 2013
Mechanism research on microRNA-669f-5p/deoxycytidylate deaminase axis mediating sevoflurane-induced cognitive
Yuan-Ping Zhong1,2, Chao Zhang2, Xue Zheng3
1Suzhou Medical College of Soochow University, Suzhou, China.
Objective:
To investigate the role of the microRNA (miRNA)-669f-5p/deoxycytidylate deaminase (Dctd) axis in sevoflurane inducing cognitive dysfunction in aged mice.
Methods:
Sixty-six C57BL/6J mice were used in the experiment model and were randomly divided into the sevoflurane group and the control group. The mice in the sevoflurane group were anesthetised with 3.4% sevoflurane, whereas those in the control group were air-treated for the same period. The study was then performed using bioinformatics sequencing, as well as in vitro and in vivo validation.
Results:
The mice in the sevoflurane group showed significant cognitive impairments in terms of a decrease in both spatial learning and memory abilities. Experimental doses of miR-669f-5p agonist exhibited no obvious effect on cognitive function following sevoflurane inhalation, but inhibiting the expression of miR-669f-5p could alleviate the impairments. Based on the results of the bioinformatics sequencing, miR-669f-5p/Dctd and the toll-like receptor (TLR) signalling pathway could be the key miRNA, gene and pathway leading to postoperative cognitive dysfunction following sevoflurane inhalation. The aged mice showed significantly increased expression of miR-669f-5p in the hippocampus following sevoflurane inhalation, and upregulating/inhibiting its expression could increase/decrease TLR expression in the hippocampus. Furthermore, miR-669f-5p could reduce the expression of the Dctd gene by binding to its 3'untranslated region.
Conclusion:
The miR-669f-5p/Dctd axis plays an important role in sevoflurane inducing cognitive dysfunction in aged mice, providing a new direction for further development of therapeutic strategies concerning the prevention and treatment of cognitive dysfunction associated with sevoflurane anaesthesia.
Insights
Sevoflurane anesthesia impairs cognitive function in aged mice by increasing microRNA (miRNA)-669f-5p, which downregulates deoxycytidylate deaminase (Dctd). Inhibiting miR-669f-5p can alleviate this sevoflurane-induced cognitive dysfunction.
Area of Science:
- Neuroscience and Pharmacology
- Molecular Biology
- Gerontology
Background:
- Sevoflurane anesthesia is associated with postoperative cognitive dysfunction (POCD), particularly in aged individuals.
- The underlying molecular mechanisms of sevoflurane-induced cognitive impairment remain incompletely understood.
- MicroRNAs (miRNAs) are emerging as critical regulators of gene expression and neuronal function.
Purpose of the Study:
- To elucidate the role of the microRNA (miRNA)-669f-5p/deoxycytidylate deaminase (Dctd) axis in sevoflurane-induced cognitive dysfunction in aged mice.
- To investigate the potential of targeting this axis for therapeutic interventions.
Main Methods:
- Establishment of a sevoflurane anesthesia model in aged C57BL/6J mice.
- Assessment of cognitive function using spatial learning and memory tests.
- Bioinformatics sequencing, in vitro, and in vivo validation of miRNA and gene expression, including toll-like receptor (TLR) signaling pathway analysis.
Main Results:
- Sevoflurane anesthesia significantly impaired spatial learning and memory in aged mice.
- Inhibition of miR-669f-5p expression alleviated sevoflurane-induced cognitive deficits.
- miR-669f-5p was upregulated in the hippocampus post-sevoflurane, directly downregulating Dctd expression and influencing TLR signaling.
Conclusions:
- The miR-669f-5p/Dctd axis is a key player in sevoflurane-induced cognitive dysfunction in aged mice.
- This axis represents a potential therapeutic target for preventing and treating cognitive impairment associated with sevoflurane anesthesia.
