Neuroprotective effect of miR-519a-3p downregulation against sevoflurane-induced cognitive dysfunction via regulating ESR1.

Background

Sevoflurane (Sevo) is widely applied in clinical anesthesia practice, and exposure to this agent has been linked to cognitive impairment.

Purpose

This study aimed to explore how microRNA-519a-3p (miR-519a-3p) contributes to Sevo-induced cognitive impairment and the molecular mechanisms involved.

Methods

A Sevo-induced anesthesia injury model was established by exposing rats to 2.5% Sevo for 6 h, and spatial learning and memory were subsequently evaluated using the Morris water maze (MWM). The expression level of miR-519a-3p was determined by RT-qPCR. CCK-8 assay, RT-qPCR, ELISA, and Western blot were respectively applied to evaluate cell viability, apoptotic gene expression, inflammatory cytokine levels, as well as protein levels of key mitochondrial dynamics and endoplasmic reticulum stress markers. A dual-luciferase reporter assay further verified the direct binding interaction between miR-519a-3p and estrogen receptor 1 (ESR1).

Results

Sevo exposure caused marked impairments in spatial learning and memory in rats, manifested as prolonged escape latency, reduced dwell time in the target quadrant, and fewer platform crossings. In vitro assays demonstrated that Sevo treatment significantly elevated miR-519a-3p expression in SH-SY5Y cells, while suppressing cell viability, accelerating apoptosis, and boosting the release of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Knockdown of miR-519a-3p markedly reversed these aberrant phenotypes both in vivo and in vitro. MiR-519a-3p inhibition restored ESR1 expression. Rescue experiments further confirmed that ESR1 knockdown attenuated the protective effects of miR-519a-3p silencing against Sevo-induced cellular damage.

Conclusions

MiR-519a-3p contributed to Sevo-induced cognitive dysfunction and cellular injury via negatively targeting ESR1.