LncRNA Neat1/miR-298-5p/Srpk1 Contributes to Sevoflurane-Induced Neurotoxicity

Sevoflurane is a widely used volatile anesthetic, that can cause long-term neurotoxicity and learning and memory impairment. Long non-coding RNAs (lncRNAs) have been demonstrated to function as key mediators in neurotoxicity. This study aimed to investigate the effects of lncRNA Neat1 on sevoflurane-induced neurotoxicity. The expression of Neat1, miR-298-5p, and Srpk1 was measured by RT-qPCR. Cell viability, cell apoptosis, inflammation markers, and reactive oxygen species (ROS) generation were examined by CCK-8, TUNEL, ELISA, and the ROS kit. The interaction between miR-298-5p and Neat1 or Srpk1 was confirmed by luciferase reporter assay. In our study, it was found that sevoflurane aggravated neurotoxicity through inhibiting cell viability and enhancing cell apoptosis, neuroinflammation, and ROS generation. Neat1 was up-regulated in sevoflurane-treated HT22 cells, and Neat1 knockdown improved sevoflurane-mediated neurotoxicity. Through the exploration of the ceRNA mechanism, we found that Neat1 bound with miR-298-5p, and Srpk1 was a direct target gene of miR-298-5p. Finally, rescue assays proved that up-regulation of Srpk1 reversed the effects of Neat1 knockdown on neurotoxicity. In conclusion, our study revealed that lncRNA Neat1 facilitated sevoflurane-stimulated neurotoxicity by sponging miR-298-5p to up-regulate Srpk1. These findings might provide novel insights into the treatment of sevoflurane-induced neurotoxicity.

Automated summary

Sevoflurane exacerbates neurotoxicity by inhibiting cell viability and promoting cell apoptosis, neuroinflammation, and ROS production. Neat1 is up-regulated in sevoflurane-treated cells, and its knockdown can improve sevoflurane-induced neurotoxicity. Through a ceRNA mechanism, it was found that Neat1 interacts with miR-298-5p to up-regulate Srpk1, ultimately contributing to sevoflurane-stimulated neurotoxicity.