Propofol, a widely used intravenous anesthetic, was previously considered as a neuroprotective agent. Recently, however, accumulating evidence suggests that it may cause neurotoxicity, especially in the development of neural stem cells (NSCs). The potential mechanisms contributing to propofol-induced neurotoxicity during neurogenesis, such as those involving microRNAs (miRNAs), are still unknown. In this study, a total of 27 differentially expressed miRNAs were identified in our initial screen and 6 miRNAs were validated by qRT-PCR. Three miRNAs were up-regulated (miR-377-5p, miR-194-3p and miR-143-5p), and three were down-regulated (miR-3583-3p, miR-466b-5p and miR-410-5p). Following gene ontology and KEGG pathway enrichment analysis, Gabbr1, Canca1b and Gabbr2, which are enriched in the GABAergic synapse pathway, were selected as genes potentially playing a role in propofol-induced neurotoxicity. Gabbr1 and Cacna1b, which are targeted by miRNAs that are up-regulated following propofol exposure, showed decreased expression at the mRNA and protein levels. Gabbr2, targeted by miRNAs that were down-regulated following treatment with propofol, was up-regulated at both the levels of mRNA and protein expression. The two clusters of miRNAs that show differential expression following propofol exposure may act in a synergistic manner to regulate several genes simultaneously during the development of NSCs. Our results may contribute to clarify the molecular mechanism and provide potential therapeutic targets for propofol induced neurotoxicity.
Keywords: MicroRNA; Neural stem cells; Neurogenesis; Propofol.
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