Downregulation of circTLK1 improves the impairments in learning and memory induced by anesthetics via regulating miR-374b-5p expression and reducing neuroinflammation.

Abstract

Background: Sevoflurane (Sev) is a common anesthetic used during surgery, but research on its induction of neurotoxicity and learning memory impairment is insufficient. This study aimed to explore the role of Circular RNA tousled like kinase 1 (circTLK1) and its target microRNA (miR)-374b-5p in Sev-induced neurotoxicity and learning memory impairment.

Methods: Mouse hippocampal neuronal HT22 cells and SD rats were treated with Sev. Levels of circTLK1 and miR-374b-5p were detected using RT-qPCR. The concentration of inflammatory factors was determined using ELISA. Cell viability and apoptosis were analyzed using CCK-8 and flow cytometry. Targeting relationship between circTLK1 and miR-374b-5p was validated using dual-luciferase reporter assays and RIP experiments. The Morris water maze test was used to assess the learning and spatial memory abilities of rats.

Results: The results indicated that Sev treatment stimulated neuroinflammation and oxidative stress while increasing circTLK1 levels and decreasing miR-374b-5p levels in both rats and HT22 cells. Silencing circTLK1 alleviated the decrease in cell viability, increased apoptosis rates, and raised concentrations of inflammatory factors caused by Sev treatment. In in vivo experiments, silencing circTLK1 was also found to counteract the oxidative stress, neuroinflammation, and learning and memory impairment induced by Sev treatment in rats. Additionally, circTLK1 was shown to interact with miR-374b-5p, and inhibiting miR-374b-5p could counteract the neuroprotective effects of si-circTLK1.

Conclusion: This research suggested that silencing circTLK1 can mitigate Sev-induced neurotoxicity and learning memory impairment by modulating miR-374b-5p.