Mechanism research on microRNA-669f-5p/deoxycytidylate deaminase axis mediating sevoflurane-induced cognitive dysfunction in aged mice

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.