Transcriptome analysis of sevoflurane exposure effects at the different brain regions.
Transcriptome analysis of sevoflurane exposure effects at the different brain regions.
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DOI：
10.1371/journal.pone.0236771
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Asahara H
中科院分区：
文献类型：
--
作者：
Yamamoto H;Uchida Y;Chiba T;Kurimoto R;Matsushima T;Inotsume M;Ishikawa C;Li H;Shiga T;Muratani M;Uchida T;Asahara H
七氟烷是最常用的挥发性麻醉剂，但其分子作用机制仍不清楚。我们假设特定基因在暴露于七氟烷的大脑中发挥调节作用。因此，我们的目的是评估七氟醚吸入的影响，并通过 RNA-seq 分析识别潜在的调控基因。八周大的小鼠暴露于七氟醚。使用 RNA-seq 分析来自内侧前额叶皮层、纹状体、下丘脑和海马体的 RNA。提取不同表达的基因并使用 Metascape 分析它们的基因本体术语。我们将这些麻醉小鼠数据与睡眠小鼠大脑皮层的转录组阵列数据进行了比较。最后，使用加权参数基因集分析（wPGSA）评估转录因子的活性。 JASPAR用于确认不同表达基因的上游序列中结合基序的存在。基因本体术语富集分析结果表明，七氟醚吸入上调大脑各区域的血管生成并下调神经分化。与熟睡小鼠大脑的比较表明，基因表达变化是麻醉小鼠特有的。七氟烷以个体基因为重点，诱导大脑所有采样部位的 Klf4 上调。 wPGSA支持KLF4作为转录因子的功能，并且KLF4结合基序存在于差异表达基因的许多调控区域中。小鼠大脑中吸入七氟醚后 Klf4 上调。 KLF4 的作用可能是阐明七氟烷诱导大脑功能改变机制的关键。
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.
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影响因子：
3.7
作者：
Ishikawa C;Li H;Ogura R;Yoshimura Y;Kudo T;Shirakawa M;Shiba D;Takahashi S;Morita H;Shiga T
通讯作者：
Shiga T
影响因子：
21.3
作者：
Jiang, Jianming;Chan, Yun-Shen;Ng, Huck-Hui
通讯作者：
Ng, Huck-Hui
七氟醚麻醉对小鼠海马的全面mRNA表达谱的影响。
影响因子：
2.9
作者：
Hayase T;Tachibana S;Yamakage M
通讯作者：
Yamakage M
影响因子：
14.9
作者：
Kawakami E;Nakaoka S;Ohta T;Kitano H
通讯作者：
Kitano H
影响因子：
56.9
作者：
Rodriques, Samuel G.;Stickels, Robert R.;Macosko, Evan Z.
通讯作者：
Macosko, Evan Z.