Determination of the Effects of Sevoflurane Anesthesia in Different Maturing Stages of the Mouse Hippocampus by Transcriptome Analysis

Abstract

Purpose: Postoperative cognitive dysfunction (POCD) is a serious complication after general anesthesia. POCD is more likely to occur in elderly patients, but the mechanism of POCD has not been fully elucidated. We hypothesized that the difference of mRNA expression profile in the brain depending on the maturing stage causes the difference in the effect of sevoflurane anesthesia. We investigated the mRNA expression profile of hippocampal cells in young mice and in aged mice under sevoflurane anesthesia using transcriptome analysis. Methods:This study was conducted after approval from our institutional animal ethics committee, the Animal Research Center of Sapporo Medical University School of Medicine (project number: 12-033). Eight mice were assigned to two groups: a young group and an aged group. Each of the 4 mice in the two groups was anesthetized with 3.5% sevoflurane for 1 hour. Subsequently, mRNA was isolated from hippocampal cells and RNA sequencing was performed on an Illumina HiSeq 2500 platform. Mapping of the quality-controlled, filter paired-end reads to mouse genomes and quantification of the expression level of each gene were performed using R software. Results:The Lhx9 gene, which is thought to be associated with neuronal inflammation, was the most highly upregulated gene in aged mice. The Epyc gene, which encodes a protein related to the phospholipase-C pathway and ERK signaling, was the most down-regulated gene in aged mice. Conclusions:The findings suggest that sevoflurane anesthesia induces neuronal inflammation via a LIMhomeodomain family related gene in aged mice and causes POCD.

Hippocampal Changes Elicited by Metabolic and Inflammatory Stressors following Prenatal Maternal Infection

“…CBLN3 is involved in the maintenance of synapse structure, and the pattern detected in the present study is aligned with the proposition that higher expression levels of CBLN3 offer protection against neuroinflammation [32]. The expression pattern of CBLN3 was similar to CALB1, including significant MIA-by-postnatal stress interaction, including a more extreme over-expression in either MIA or fasting followed by Poly(I:C).…”