Abstract
Although propofol exerts toxic effects on the developing central nervous system (CNS), it remains a first-choice anesthetic in the pediatric population. Astrocytes represent a major glial cell population whose role in CNS development is widely appreciated and that has been recently shown to be mediated in large part by microRNAs (miRNAs). In contrast, relatively little is known about the roles of miRNAs in developing astrocytes during propofol treatment. Here, miRNA microarray was used to profile fluctuations in miRNA expression in immature hippocampal astrocytes in response to propofol treatment, and results were subsequently validated using quantitative real-time polymerase chain reaction. Predictive analysis of genes targeted by propofol-regulated miRNAs indicated enrichment of genes in the gene ontology (GO) nervous system development and differentiation category, and in the Kyoto encyclopedia of genes and genomes (KEGG) apoptotic pathway category. A total of 24 (10 short-term dosage and 14 long-term dosage) miRNAs were significantly regulated, one of which was rno-miR-665. Ectopic overexpression and silencing of rno-miR-665 demonstrated its role in the neurotoxic effects of propofol on hippocampal immature astrocytes. We present evidence that the role of rno-miR-665 in anesthesia-induced disturbances in astroglia development may involve direct downregulation of the anti-apoptotic gene Bcl2l1, and subsequent increased caspase-3-mediated apoptosis. Our results shed light on the anesthetic mechanism of propofol and have implications for its use in the clinical setting.