Neuroprotective effect of miR-204-5p downregulation against isoflurane-induced learning and memory impairment via targeting EphB2 and inhibiting neuroinflammation.

Abstract

Isoflurane, one of the most commonly used inhalational anesthetics, is usually used in surgery patients and often causes long-term learning and memory impairment. The aim of this study was to explore the role of microRNA-204-5p (miR-204-5p) in isoflurane-induced learning and memory impairment in rats. The Morris Water Maze (MWM) test was used to estimate the spatial learning and memory abilities of laboratory rats. Enzyme-linked immunosorbent assay (ELISA) was used to determine interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) concentrations in the hippocampal tissues. The expression level of miR-204-5p was determined by using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The potential target genes of miR-204-5p were predicted and verified by the TargetScan and dual-luciferase reporter assay, respectively. Isoflurane-induced rats showed significantly higher neurological function scores, higher escape latency and shorter time spent in the original quadrant. Isoflurane could significantly induce neuroinflammation, and the expression of miR-204-5p was increased in the hippocampal tissue of rats exposed to isoflurane. Moreover, downregulation of miR-204-5p attenuated the effect of isoflurane treatment on the escape latency and the time in the original quadrant, and inflammatory cytokines level was downregulated by inhibiting the expression of miR-204-5p. EphB2 was verified as a direct target gene of miR-204-5p. Downregulated miR-204-5p exerts protective effects against isoflurane-induced learning and memory impairment via targeting EphB2 and inhibiting neuroinflammation. MiR-204-5p could serve as a potential therapeutic target for the lightening of cognitive dysfunction induced by isoflurane.