Identification of gene expression change associated with isoflurane anesthesia and neurocognitive disorders using bioinformatics methods

Abstract

Background

Isoflurane, a commonly used anesthetic, has been linked to neurocognitive dysfunction (NCD). However, the precise relationship between isoflurane anesthesia and NCD remains unclear.

Methods

Datasets related to isoflurane anesthesia were obtained from a public database. The hub genes of isoflurane anesthesia were selected using logistic regression with the least absolute shrinkage and selection operator (LASSO). Human neuroblastoma cell line SH-SY5Y was induced to differentiate into terminal neuron-like cells.

Results

The signaling pathways involved in isoflurane anesthesia and NCD were subjected to analysis, resulting in the identification of 35 signaling pathways, including the PI3K/AKT pathway, the AGE-RAGE signaling pathway and the apelin signaling pathway, which were found to be associated with both NCD and isoflurane anesthesia. A total of nine cross-expressed genes (Nfe2l2, Fgf2, Edn1, Spp1, Hmox1, Picalm, Gnb5, Eif2s1 and Gls) were identified between isoflurane anesthesia and NCD. The LASSO logistic regression model was employed to identify three hub genes (Fgf2, Gnb5, Spp1). The expression of these three hub genes was validated using other expression datasets. In human neuron-like cells, isoflurane also significantly affected the expression of three corresponding human homologous genes. The expression trends of these three genes in human cells were consistent with the expression in rat brains after isoflurane treatment, providing further evidence for the rationality of the three hub genes.

Conclusions

The present study revealed key candidate genes and related functional signaling pathways through bioinformatics analysis and cell experiments, which may serve as the basis for isoflurane-related NCD.