Identification of Prefrontal Cortex and Amygdala Expressed Genes Associated With Sevoflurane Anesthesia on Non-human Primate

Abstract

Clinical trials and animal studies have indicated that long-term use or multiple administrations of anesthesia may lead to fine motor impairment in the developing brain. Most studies on anesthesia-induced neurotoxicity have focused on the hippocampus and prefrontal cortex (PFC); however, the role of other vital encephalic regions, such as the amygdala, is still unclear. Herein, we focused on sevoflurane, the most commonly used volatile anesthetic in infants, and performed a transcriptional analysis of the PFC and amygdala of macaques after multiple exposures to the anesthetic by RNA sequencing. The overall, overlapping, and encephalic region-specific transcriptional patterns were separately analyzed to reveal their functions and differentially expressed gene sets that were influenced by sevoflurane. Specifically, functional, protein–protein interaction, neighbor gene network, and gene set enrichment analyses were performed. Further, we built the basic molecular feature of the amygdala by comparing it to the PFC. In comparison with the amygdala’s changing pattern following sevoflurane exposure, functional annotations of the PFC were more enriched in glial cell-related biological functions than in neuron and synapsis development. Taken together, transcriptional studies and bioinformatics analyses allow for an improved understanding of the primate PFC and amygdala.

General anesthetic action profile on the human prefrontal cortex cells through comprehensive single-cell RNA-seq analysis

“… 26 Moreover, the dysregulated genes/pathways associated with sevoflurane exposure were also reported in rhesus macaques. 27 However, the work reported here was the first-line evidence on transcriptome changes in human fetal prefrontal cortex cells following general anesthetic exposure using scRNA sequencing technique, providing accurate identification of gene expression patterns within each cell type. Unlike enrichment of KLF4 and NFATC2 in animals (Yamamoto et al., 2020; Cheng et al., 2022), our study identified enrichment in KLF6, KLF10, and NFATC4 in human PFC cells that could be due to species variation.…”

The effect of sevoflurane exposure on cell‐type‐specific changes in the prefrontal cortex in young mice

“…Sevoflurane, commonly used for pediatric surgeries, has been implicated in neurotoxicity in various brain regions with multiple neonatal exposures (Sun et al., 2022). The prefrontal cortex (PFC), a region vulnerable to anesthetic‐induced developmental neurotoxicity, plays a crucial role in cognitive functions such as social behavior, working memory, decision‐making, and fine motor skills (Cheng et al., 2022). Additionally, the PFC exhibits neuroplasticity during postnatal life, potentially contributing to neurotoxicity and neuropsychiatric disorders (Miller et al., 2002).…”