Sevoflurane upregulates neuron death process-related Ddit4 expression by NMDAR in the hippocampus

Abstract

Postoperative cognitive dysfunction (POCD) is a serious and common complication induced by anesthesia and surgery. Neuronal apoptosis induced by general anesthetic neurotoxicity is a high-risk factor. However, a comprehensive analysis of general anesthesia-regulated gene expression patterns and further research on molecular mechanisms are lacking. Here, we performed bioinformatics analysis of gene expression in the hippocampus of aged rats that received sevoflurane anesthesia in GSE139220 from the GEO database, found a total of 226 differentially expressed genes (DEGs) and investigated hub genes according to the number of biological processes in which the genes were enriched and performed screening by 12 algorithms with cytoHubba in Cytoscape. Among the screened hub genes, Agt , Cdkn1a , Ddit4 , and Rhob are related to the neuronal death process. We further confirmed that these genes, especially Ddit4 , were upregulated in the hippocampus of aged mice that received sevoflurane anesthesia. NMDAR , the core target receptor of sevoflurane, rather than GABA A R , mediates the sevoflurane regulation of DDIT4 expression. Our study screened sevoflurane-regulated DEGs and focused on the neuronal death process to reveal DDIT4 as a potential target mediated by NMDAR , which may provide a new target for the treatment of sevoflurane neurotoxicity.

Fgf2 and Ptpn11 play a role in cerebral injury caused by sevoflurane anesthesia

“…In this study, the sevoflurane anesthesia brain tissue datasets GSE139220 and GSE141242 were obtained from the gene expression omnibus, generated with the platform GPL22388. GSE139220 [ 18 ] consists of 3 post-sevoflurane anesthesia brain tissue samples and 3 normal brain tissue samples, GSE141242 includes 3 post-sevoflurane anesthesia brain tissue samples and 3 normal brain tissue samples.…”