Silencing CircHIPK3 improves sevoflurane-explore learning and memory dysfunction and nerve damage via enhancing miR-338-3p

Xiuli Li; Xuefei Li; Yinan Liang

doi:10.1093/toxres/tfae132

Silencing CircHIPK3 improves sevoflurane-explore learning and memory dysfunction and nerve damage via enhancing miR-338-3p

Toxicol Res (Camb). 2024 Aug 19;13(4):tfae132. doi: 10.1093/toxres/tfae132. eCollection 2024 Aug.

Authors

Xiuli Li¹, Xuefei Li², Yinan Liang³

Affiliations

¹ Department of Anesthesiology, Pengzhou People's Hospital , No. 255 South Third Ring Road, Pengzhou 611930, China.
² Department of Anesthesiology, The Second People's Hospital of Pidu District of Chengdu, No. 86 Southeast Section of the Second Ring Road, Pidu District, Chengdu 611733, China.
³ Department of Anesthesiology, School of Clinical Medicine & The First Affiliated Hospital of Chengdu Medical College, No. 278 Middle Baoguang Avenue, Xindu District, Chengdu 610500, China.

PMID: 39165832
PMCID: PMC11331635 (available on 2025-08-19)
DOI: 10.1093/toxres/tfae132

Abstract

Background: Sevoflurane (Sev), a widely used volatile anesthetic, can cause neurotoxicity, and impair learning and memory.

Objective: This study investigates the role and mechanisms of circHIPK3 in Sev-exposed neurotoxicity and learning and memory impairment.

Methods: SD rats and hippocampal neuronal cells were exposed to Sev. RT-qPCR analysis of circHIPK3 and miR-338-3p levels. MWM test was performed to examine the behavioral changes in rats. The levels of circHIPK3 and miR-338-3p levels were investigated using RT-qPCR. ELISA assay to analyze the expression of pro-inflammatory factors. CCK-8, flow cytometry, and commercial ROS assay kits were analyzed to detect cell viability, apoptosis, and ROS production. DLR and RIP assays validate circHIPK3 binding to miR-338-3p.

Results: Sev increased circHIPK3 expression in rat hippocampal tissue as well as in neuronal cells but decreased miR-338-3p levels compared to controls. circHIPK3 binding to miR-338-3p. Furthermore, silencing of circHIPK3 rats attenuated Sev-induced decline in learning and memory functions . silencing circHIPK3 also reduced Sev-induced secretion of inflammatory factors in rat and neuronal cells. Reducing circHIPK3 partially reversed the Sev-induced decrease in cell viability, increased apoptosis, and overproduction of ROS. However, the inhibitory effect of circHIPK3 on Sev neurotoxicity was restored upon downregulation of miR-338-3p.

Conclusion: Collectively, silencing circHIPK3 alleviates Sev exposure-induced learning and memory deficits and neurotoxicity by enhancing miR-338-3p expression.

Keywords: Sevoflurane; circHIPK3; miR-338-3p.