miR-455-3p alleviates propofol-induced neurotoxicity by reducing EphA4 expression in developing neurons
Xiaojuan Zhu1, Huifang Li1, Ming Tian1
1Department of Anesthesiology, The First People's Hospital of Kashi, Kashgar City, China.
Insights
Propofol harms developing neurons by decreasing miR-455-3p. Upregulating miR-455-3p (microRNA-455-3p) protects against propofol neurotoxicity by reducing EphA4 expression.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Propofol is a common anesthetic in pediatric patients.
- Propofol exposure can lead to neurotoxicity in developing neurons.
- MicroRNAs play crucial roles in neuronal development and function.
Purpose of the Study:
- To investigate the protective role of miR-455-3p against propofol-induced neurotoxicity in developing rat hippocampal neurons.
- To elucidate the molecular mechanism underlying this protective effect, focusing on the interaction between miR-455-3p and EphA4.
Main Methods:
- Primary hippocampal neurons were isolated from Sprague-Dawley rats.
- Neurons were exposed to varying concentrations of propofol.
- Cell viability, miR-455-3p and EphA4 expression levels, and apoptosis were assessed.
- The interaction between miR-455-3p and EphA4 was validated using luciferase reporter assays and knockdown experiments.
Main Results:
- Propofol exposure significantly reduced neuronal viability and increased apoptosis.
- Propofol decreased miR-455-3p expression while increasing EphA4 levels.
- Overexpression of miR-455-3p protected neurons against propofol-induced neurotoxicity and apoptosis.
- miR-455-3p directly targets EphA4, and its knockdown reversed the protective effects.
Conclusions:
- Propofol induces neurotoxicity in developing hippocampal neurons by suppressing miR-455-3p.
- miR-455-3p exerts a neuroprotective effect by downregulating EphA4 expression.
- miR-455-3p represents a potential therapeutic target for mitigating propofol-induced neurotoxicity.
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.
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