miR-455-3p alleviates propofol-induced neurotoxicity by reducing EphA4 expression in developing neurons

Abstract

Purpose

Propofol, an aesthetic agent in paediatric patients, results in neurotoxicity in the developing neurons. To reduce side effects of propofol, the protective role of miR-455-3p (microRNA-455-3p) in developing rat brain was investigated.

Materials and methods

Primary hippocampal neurons were isolated from postnatal day 1 or 2 SD (Sprague-Dawley) rats. The neurons were exposed to various concentrations of propofol (0, 10, 30, or 50 μM) for 6 h. Propofol-induced cell viability was assessed by MTT assay, expression levels of miR-455-3p and EphA4 (erythropoietin-producing hepatocellular A4) in propofol-induced neurons were determined using qRT-PCR and western blot, respectively. Binding ability between miR-455-3p and EphA4 was predicted, and then validated by luciferase reporter assay. Neurons expressing miR-455-3p mimics, were treated with 50 μM propofol for 6 h, and apoptosis status was evaluated by flow cytometry.

Results

Exposure to propofol significantly decreased cell viability of developing neurons isolated from neonatal rats. Propofol decreased miR-455-3p expression, while increased EphA4 level in the neurons. miR-455-3p mimics increased propofol-induced reduce in cell viability, and attenuated propofol-induced cell apoptosis of neurons. MiR-455-3p could target EphA4, and decreased expression of EphA4 in neurons exposure to propofol. EphA4 knockdown counteracted with the promotive effects of propofol on cell viability and apoptosis of neurons.

Conclusion

Propofol treatment induces neurotoxicity and suppresses miR-455-3p levels in the developing hippocampal neurons. However, miR-455-3p could alleviate such neurotoxicity by reducing EphA4 expression, provided new insights into miR-455-3p as novel therapeutic target to prevent propofol-induced damages from bench to clinic.

Keywords:

• miR-455-3p
• EphA4
• propofol
• neurotoxicity
• apoptosis
• developing neurons

Author contributions

XZ, HL and MZ designed the study, supervised the data collection, analysed the data, MT interpreted the data and prepare the manuscript for publication, SZ and YH supervised the data collection, analysed the data and reviewed the draft of the manuscript. All authors have read and approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data generated or analysed during this study are included in this published article.