Translatome and transcriptome profiling of neonatal mice hippocampus exposed to sevoflurane anesthesia

Exposure to anesthesia in early life may cause severe damage to the brain and lead to cognitive impairment. The underlying mechanisms, which have only been investigated in a limited scale, remains largely elusive. We performed translatome and transcriptome sequencing together for the first time in hippocampus of neonatal mice that were exposed to sevoflurane. We treated a group of neonatal mice with 2.5 % sevoflurane for 2 h on day 6, 7, 8, 9 and treated another group on day 6, 7. We performed behavioral study after day 30 for both groups and the control to evaluate the cognitive impairment. On day 36, we collected translatome and transcriptome from the hippocampus in the two groups, compared the gene expression levels between the groups and the control, and validated the results with RT-qPCR. We identified 1750 differentially expressed genes (DEGs) from translatome comparison and 1109 DEGs from transcriptome comparison. As expected, translatome-based DEGs significantly overlapped with transcriptome-based DEGs, and functional enrichment analysis generated similar enriched cognition-related GO terms and KEGG pathways. However, for many genes like Hspa5, their alterations in translatome differed remarkably from those in transcriptome, and Western blot results were largely concordant with the former, suggesting that translational regulation plays a significant role in cellular response to sevoflurane. Our study revealed global alterations in translatome and transcriptome of mice hippocampus after neonatal exposure to sevoflurane anesthesia and highlighted the importance of translatome analysis in understanding the mechanisms responsible for anesthesia-induced cognitive impairment.