Single-cell transcriptomics reveals the mechanism of long-term neurodevelopmental toxicity following sevoflurane...

Prolonged exposure to general anesthetics during early development has been associated with neurobehavioral deficits. Sevoflurane, a commonly used pediatric anesthetic, may disrupt cortical maturation, particularly in the prefrontal cortex (PFC) which plays a critical integrative and regulatory role in cognitive and motor functions. In this study, the long-term effects of neonatal sevoflurane exposure were examined using a mouse model, complemented by analysis of single-cell RNA sequencing data from human embryonic PFC (GSE196239). Behavioral assays showed that mice exposed to sevoflurane at postnatal day 7 exhibited persistent impairments in fine motor ability and spatial memory in adulthood. Transcriptomic analysis showed that sevoflurane induced widespread gene expression alterations without changing the major cell-type composition. Through enrichment analysis, dysregulation of pathways related to cell shape was identified. Consistent with these transcriptomic findings, reduced dendritic complexity was observed in sevoflurane-treated neurons by immunofluorescence. Notably, microtubule-associated protein 2 (MAP2), a key structural protein in dendrites, was significantly reduced at the protein level without a corresponding decrease in mRNA expression, suggesting the involvement of post-transcriptional regulation. Together, these findings suggest that prolonged neonatal sevoflurane exposure may impair neuronal maturation and dendritic architecture, and provide molecular insights into the long-term cognitive and motor alterations associated with neonatal sevoflurane exposure.