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Transcriptome analysis of sevoflurane exposure effects at the different brain regions

BACKGROUNDS: 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 pot...

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Autores principales: Yamamoto, Hiroto, Uchida, Yutaro, Chiba, Tomoki, Kurimoto, Ryota, Matsushima, Takahide, Inotsume, Maiko, Ishikawa, Chihiro, Li, Haiyan, Shiga, Takashi, Muratani, Masafumi, Uchida, Tokujiro, Asahara, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737892/
https://www.ncbi.nlm.nih.gov/pubmed/33320849
http://dx.doi.org/10.1371/journal.pone.0236771
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author Yamamoto, Hiroto
Uchida, Yutaro
Chiba, Tomoki
Kurimoto, Ryota
Matsushima, Takahide
Inotsume, Maiko
Ishikawa, Chihiro
Li, Haiyan
Shiga, Takashi
Muratani, Masafumi
Uchida, Tokujiro
Asahara, Hiroshi
author_facet Yamamoto, Hiroto
Uchida, Yutaro
Chiba, Tomoki
Kurimoto, Ryota
Matsushima, Takahide
Inotsume, Maiko
Ishikawa, Chihiro
Li, Haiyan
Shiga, Takashi
Muratani, Masafumi
Uchida, Tokujiro
Asahara, Hiroshi
author_sort Yamamoto, Hiroto
collection PubMed
description BACKGROUNDS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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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spelling pubmed-77378922021-01-08 Transcriptome analysis of sevoflurane exposure effects at the different brain regions Yamamoto, Hiroto Uchida, Yutaro Chiba, Tomoki Kurimoto, Ryota Matsushima, Takahide Inotsume, Maiko Ishikawa, Chihiro Li, Haiyan Shiga, Takashi Muratani, Masafumi Uchida, Tokujiro Asahara, Hiroshi PLoS One Research Article BACKGROUNDS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Public Library of Science 2020-12-15 /pmc/articles/PMC7737892/ /pubmed/33320849 http://dx.doi.org/10.1371/journal.pone.0236771 Text en © 2020 Yamamoto et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Yamamoto, Hiroto
Uchida, Yutaro
Chiba, Tomoki
Kurimoto, Ryota
Matsushima, Takahide
Inotsume, Maiko
Ishikawa, Chihiro
Li, Haiyan
Shiga, Takashi
Muratani, Masafumi
Uchida, Tokujiro
Asahara, Hiroshi
Transcriptome analysis of sevoflurane exposure effects at the different brain regions
title Transcriptome analysis of sevoflurane exposure effects at the different brain regions
title_full Transcriptome analysis of sevoflurane exposure effects at the different brain regions
title_fullStr Transcriptome analysis of sevoflurane exposure effects at the different brain regions
title_full_unstemmed Transcriptome analysis of sevoflurane exposure effects at the different brain regions
title_short Transcriptome analysis of sevoflurane exposure effects at the different brain regions
title_sort transcriptome analysis of sevoflurane exposure effects at the different brain regions
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737892/
https://www.ncbi.nlm.nih.gov/pubmed/33320849
http://dx.doi.org/10.1371/journal.pone.0236771
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