Department of Systems BioMedicine, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Department of Anesthesiology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
PLoS One. 2020 Dec 15;15(12):e0236771. doi: 10.1371/journal.pone.0236771. eCollection 2020.
Sevoflurane is a most frequently used volatile anesthetics, but its molecular mechanisms of action remain unclear. We hypothesized that specific genes play regulatory roles in brain exposed to sevoflurane. Thus, we aimed to evaluate the effects of sevoflurane inhalation and identify potential regulatory genes by RNA-seq analysis.
Eight-week old mice were exposed to sevoflurane. RNA from medial prefrontal cortex, striatum, hypothalamus, and hippocampus were analysed using RNA-seq. Differently expressed genes were extracted and their gene ontology terms were analysed using Metascape. These our anesthetized mouse data and the transcriptome array data of the cerebral cortex of sleeping mice were compared. Finally, the activities of transcription factors were evaluated using a weighted parametric gene set analysis (wPGSA). JASPAR was used to confirm the existence of binding motifs in the upstream sequences of the differently expressed genes.
The gene ontology term enrichment analysis result suggests that sevoflurane inhalation upregulated angiogenesis and downregulated neural differentiation in each region of brain. The comparison with the brains of sleeping mice showed that the gene expression changes were specific to anesthetized mice. Focusing on individual genes, sevoflurane induced Klf4 upregulation in all sampled parts of brain. wPGSA supported the function of KLF4 as a transcription factor, and KLF4-binding motifs were present in many regulatory regions of the differentially expressed genes.
Klf4 was upregulated by sevoflurane inhalation in the mouse brain. The roles of KLF4 might be key to elucidating the mechanisms of sevoflurane induced functional modification in the brain.
七氟醚是最常用的挥发性麻醉剂之一，但作用机制尚不清楚。我们假设特定基因在暴露于七氟醚的大脑中发挥调节作用。因此，我们旨在通过 RNA-seq 分析评估七氟醚吸入的影响并鉴定潜在的调节基因。
将 8 周龄的小鼠暴露于七氟醚中。使用 RNA-seq 分析来自中前额叶皮质、纹状体、下丘脑和海马的 RNA。提取差异表达基因，并使用 Metascape 分析其基因本体论术语。将我们麻醉小鼠的数据与睡眠小鼠大脑皮层的转录组芯片数据进行比较。最后，使用加权参数基因集分析 (wPGSA) 评估转录因子的活性。使用 JASPAR 确认差异表达基因上游序列中存在结合基序。
基因本体论术语富集分析结果表明，七氟醚吸入在上皮形成和神经分化方面在大脑的各个区域中上调。与睡眠小鼠的大脑相比，基因表达变化是麻醉小鼠特有的。关注个别基因，七氟醚诱导所有取样脑区的 Klf4 上调。wPGSA 支持 KLF4 作为转录因子的功能，差异表达基因的许多调节区域存在 KLF4 结合基序。
Klf4 被七氟醚吸入在小鼠大脑中上调。KLF4 的作用可能是阐明七氟醚诱导大脑功能修饰机制的关键。
