Transcriptomic analysis reveals the molecular mechanism of Alzheimer-related neuropathology induced by sevoflurane in mice.

Abstract

Anesthetics could induce cognitive dysfunctions, such as Alzheimer's disease in humans or mice. However, the precise molecular mechanism is unclear. Sevoflurane is a common anesthetic widely used in clinical practice. Here, we demonstrated the induction of cognitive dysfunction induced by Sev in mice to corroborate the signaling pathway and the differentially expressed genes (DEGs) followed by analyzing their functions. The cognitive function of mice was measured by the Morris water maze test. Transcriptomic data were annotated with Illumina HiSeq. 2000. Further, the changes in related proteins or genes were analyzed by western blotting and real-time quantitative polymerase chain reaction. Our results showed that Sev could cause a decline in cognitive competence in mice. The transcriptomic data indicated that adding up to 566 genes were upregulated and 1073 genes were downregulated. The genes of Plin4, Lcn2, Lrg1, Foxf1, and Ctla2a were significantly upregulated, while the genes of Arc, Npas4, Egr2, Hes5, and Cdh9 were downregulated dramatically. The Gene Ontology term with the highest enrichment of DEGs are involved in the regulation of cellular and macromolecule metabolism and cation and nucleic acid binding, respectively. The Kyoto encyclopedia of genes and genomes analysis indicated that the mitogen-activated protein kinases (MAPK) pathway was one of the most important metabolic pathways. In addition, the metabolic pathways related to cognitive function, such as the nervous system and neurodegenerative disease showed significant changes. Furthermore, we found that p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase of the MAPK signaling pathway played important roles in this process. In conclusion, these results provide the first important clues for identifying the DEGs and signaling pathways in the hippocampus due to a Sev-induced cognitive deficiency in mice.