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Neuroprotective effect of miR-519a-3p downregulation against sevoflurane-induced cognitive dysfunction via regulating
Weiwei Lin1, Dan Yu2, Xiating Shi3
1Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital (Affiliated to Fuzhou University), Fuzhou 350000, China.
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.
Insights
Sevoflurane exposure impairs cognitive function by increasing microRNA-519a-3p (miR-519a-3p) levels, which targets estrogen receptor 1 (ESR1). Silencing miR-519a-3p protects against sevoflurane-induced cognitive and cellular damage.
Area of Science:
- Neuroscience
- Molecular Biology
- Anesthesiology
Background:
- Sevoflurane (Sevo) is a common anesthetic agent.
- Sevo exposure is associated with cognitive impairment.
Purpose of the Study:
- Investigate the role of microRNA-519a-3p (miR-519a-3p) in Sevo-induced cognitive impairment.
- Elucidate the underlying molecular mechanisms.
Main Methods:
- Established a Sevo-induced anesthesia injury model in rats.
- Assessed spatial learning and memory using the Morris water maze (MWM).
- Quantified miR-519a-3p expression via RT-qPCR and analyzed cellular effects (viability, apoptosis, inflammation, mitochondrial and ER stress markers) using CCK-8, RT-qPCR, ELISA, and Western blot.
- Verified the interaction between miR-519a-3p and estrogen receptor 1 (ESR1) using a dual-luciferase reporter assay.
Main Results:
- Sevo exposure impaired rat spatial learning and memory.
- In vitro, Sevo increased miR-519a-3p expression, reduced cell viability, increased apoptosis, and elevated inflammatory cytokines (IL-6, TNF-α).
- miR-519a-3p knockdown reversed Sevo-induced deficits, restored ESR1 expression, and protected against cellular damage, with ESR1 knockdown attenuating these protective effects.
Conclusions:
- MiR-519a-3p exacerbates Sevo-induced cognitive dysfunction and cellular injury.
- This occurs through the negative regulation of estrogen receptor 1 (ESR1).
