Exosomal miR-381-3p derived from astrocytes targets neuronal CDK1 to resist propofol-induced neuronal damage in vitro.

Propofol, a widely utilized general anesthetic, can result in developmental neurotoxicity. Previous studies suggest that astrocytes-derived exosomes (ADEs) carrying microRNAs (miRNAs), facilitating neuronal protection. Nevertheless, the underlying mechanism by which miRNAs in ADEs promoting protective effect for propofol-induced neuronal damage remains unknown. Thus, this investigation aims to explore the mechanisms that astrocytes resist propofol-induced neuron injury. Primary neurons and astrocytes were extracted from the hippocampus of mouse embryonic brain. The influence of propofol on neuronal apoptosis were evaluated utilizing a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. To analyze synaptic growth in neurons, immunofluorescence staining for the evaluation of neurite length was conducted. Differentially expressed miRNAs in primary mouse astrocytes were identified through miRNA sequencing, followed by validation using quantitative polymerase chain reaction (qPCR). Luciferase reporter assays, qPCR and western blotting were conducted to explore the effects of miR-381-3p on cyclin-dependent kinase 1 (CDK1) expression. We demonstrated that ADEs mitigated the neuronal damage caused by propofol. MiRNA sequencing revealed a significant upregulation of miR-381-3p within ADEs. Moreover, CDK1 was recognized as the downstream target gene of miR-381-3p. By targeting CDK1, miR-381-3p can counteract propofol-induced neuronal damage. Notably, knockdown of miR-381-3p in astrocytes distinctly diminished the neuroprotective effects of ADEs. Exosomal miR-381-3p derived from astrocytes targets neuronal CDK1 to mitigate propofol-induced neuronal damage.