Single-nucleus transcriptomics of hippocampus in developmental sevoflurane neurotoxicity

Developmental neurotoxicity induced by repeated exposures to general anesthetics has raised significant concern. Sevoflurane is the most widely used anesthetic for pediatric surgery. We previously showed that multiple neonatal exposures to sevoflurane led to behavioral and cognitive disorders, but the lack of cell type-specific resource has limited the understanding of its mechanism. Here, we conducted the single-nucleus RNA sequencing (snRNA-seq) study to reveal the cellular atlas of female mice hippocampus during developmental sevoflurane neurotoxicity when compared with normal physiological controls. We identified 13 hippocampal cell types with novel specific marker genes. Multiple neonatal sevoflurane exposures altered the ligand-receptor interactomes among different hippocampal cell types. The majority of the differentially expressed genes between the sevoflurane exposure group and the control group were unique to specific cell types. Altogether, this snRNA-seq study provides a comprehensive resource for the hippocampal cells and developmental sevoflurane neurotoxicity.