Up-regulation of miR-20a ameliorates sevoflurane anesthesia-induced cognitive impairment in rats by targeting EphA4

Purpose: To evaluate the role of miR-20a in sevoflurane (SEV)-induced cognitive impairment in rats and to elucidate the mechanism of action. Methods: A SEV-induced cognitive impairment rat model was developed. The Morris water maze test and fear assay were carried out to assess impaired learning and memory. A cellular SEV-impaired model was developed and the miR-20a level was measured in the animal and cellular models. TUNEL staining and immunoblot assay were performed to determine the SEV effect on apoptosis. Bioinformatic analysis and luciferase assay were conducted to identify the target of miR-20a action. A rescue assay involving miR-20a overexpression in cellular and animal models was developed and used to evaluate function of miR-20a in cognitive defects. Results: The rats showed significant cognitive impairment upon SEV treatment, which inhibited the expression of miR-20a and promoted neuronal apoptosis. Further findings identified EphA4 as a target of miR-20a, which regulates its expression. Overexpression of miR-20a in rats effectively reduced cognitive dysfunction and apoptosis of hippocampus somatic cells caused by SEV treatment. Conclusion: Evidently, miR-20a ameliorates SEV anesthesia-induced cognitive impairment in rats and thus has the potential to serve as a therapeutic target for the treatment of post-operative cognitive dysfunction.