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Microarray analysis of gene expression in the diacylglycerol kinase η knockout mouse brain

We have revealed that diacylglycerol kinase η (DGKη)-knockout (KO) mice display bipolar disorder (BPD) remedy-sensitive mania-like behaviors. However, the molecular mechanisms causing the mania-like abnormal behaviors remain unclear. In the present study, microarray analysis was performed to determi...

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Autores principales: Komenoi, Suguru, Suzuki, Yuji, Asami, Maho, Murakami, Chiaki, Hoshino, Fumi, Chiba, Sohei, Takahashi, Daisuke, Kado, Sayaka, Sakane, Fumio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597918/
https://www.ncbi.nlm.nih.gov/pubmed/31297456
http://dx.doi.org/10.1016/j.bbrep.2019.100660
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author Komenoi, Suguru
Suzuki, Yuji
Asami, Maho
Murakami, Chiaki
Hoshino, Fumi
Chiba, Sohei
Takahashi, Daisuke
Kado, Sayaka
Sakane, Fumio
author_facet Komenoi, Suguru
Suzuki, Yuji
Asami, Maho
Murakami, Chiaki
Hoshino, Fumi
Chiba, Sohei
Takahashi, Daisuke
Kado, Sayaka
Sakane, Fumio
author_sort Komenoi, Suguru
collection PubMed
description We have revealed that diacylglycerol kinase η (DGKη)-knockout (KO) mice display bipolar disorder (BPD) remedy-sensitive mania-like behaviors. However, the molecular mechanisms causing the mania-like abnormal behaviors remain unclear. In the present study, microarray analysis was performed to determine global changes in gene expression in the DGKη-KO mouse brain. We found that the DGKη-KO brain had 43 differentially expressed genes and the following five affected biological pathways: “neuroactive ligand-receptor interaction”, “transcription by RNA polymerase II”, “cytosolic calcium ion concentration”, “Jak-STAT signaling pathway” and “ERK1/2 cascade”. Interestingly, mRNA levels of prolactin and growth hormone, which are augmented in BPD patients and model animals, were most strongly increased. Notably, all five biological pathways include at least one gene among prolactin, growth hormone, forkhead box P3, glucagon-like peptide 1 receptor and interleukin 1β, which were previously implicated in BPD. Consistent with the microarray data, phosphorylated ERK1/2 levels were decreased in the DGKη-KO brain. Microarray analysis showed that the expression levels of several glycerolipid metabolism-related genes were also changed. Liquid chromatography-mass spectrometry revealed that several polyunsaturated fatty acid (PUFA)-containing phosphatidic acid (PA) molecular species were significantly decreased as a result of DGKη deficiency, suggesting that the decrease affects PUFA metabolism. Intriguingly, the PUFA-containing lysoPA species were markedly decreased in DGKη-KO mouse blood. Taken together, our study provides not only key broad knowledge to gain novel insights into the underlying mechanisms for the mania-like behaviors but also information for developing BPD diagnostics.
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spelling pubmed-65979182019-07-11 Microarray analysis of gene expression in the diacylglycerol kinase η knockout mouse brain Komenoi, Suguru Suzuki, Yuji Asami, Maho Murakami, Chiaki Hoshino, Fumi Chiba, Sohei Takahashi, Daisuke Kado, Sayaka Sakane, Fumio Biochem Biophys Rep Research Article We have revealed that diacylglycerol kinase η (DGKη)-knockout (KO) mice display bipolar disorder (BPD) remedy-sensitive mania-like behaviors. However, the molecular mechanisms causing the mania-like abnormal behaviors remain unclear. In the present study, microarray analysis was performed to determine global changes in gene expression in the DGKη-KO mouse brain. We found that the DGKη-KO brain had 43 differentially expressed genes and the following five affected biological pathways: “neuroactive ligand-receptor interaction”, “transcription by RNA polymerase II”, “cytosolic calcium ion concentration”, “Jak-STAT signaling pathway” and “ERK1/2 cascade”. Interestingly, mRNA levels of prolactin and growth hormone, which are augmented in BPD patients and model animals, were most strongly increased. Notably, all five biological pathways include at least one gene among prolactin, growth hormone, forkhead box P3, glucagon-like peptide 1 receptor and interleukin 1β, which were previously implicated in BPD. Consistent with the microarray data, phosphorylated ERK1/2 levels were decreased in the DGKη-KO brain. Microarray analysis showed that the expression levels of several glycerolipid metabolism-related genes were also changed. Liquid chromatography-mass spectrometry revealed that several polyunsaturated fatty acid (PUFA)-containing phosphatidic acid (PA) molecular species were significantly decreased as a result of DGKη deficiency, suggesting that the decrease affects PUFA metabolism. Intriguingly, the PUFA-containing lysoPA species were markedly decreased in DGKη-KO mouse blood. Taken together, our study provides not only key broad knowledge to gain novel insights into the underlying mechanisms for the mania-like behaviors but also information for developing BPD diagnostics. Elsevier 2019-06-25 /pmc/articles/PMC6597918/ /pubmed/31297456 http://dx.doi.org/10.1016/j.bbrep.2019.100660 Text en © 2019 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Komenoi, Suguru
Suzuki, Yuji
Asami, Maho
Murakami, Chiaki
Hoshino, Fumi
Chiba, Sohei
Takahashi, Daisuke
Kado, Sayaka
Sakane, Fumio
Microarray analysis of gene expression in the diacylglycerol kinase η knockout mouse brain
title Microarray analysis of gene expression in the diacylglycerol kinase η knockout mouse brain
title_full Microarray analysis of gene expression in the diacylglycerol kinase η knockout mouse brain
title_fullStr Microarray analysis of gene expression in the diacylglycerol kinase η knockout mouse brain
title_full_unstemmed Microarray analysis of gene expression in the diacylglycerol kinase η knockout mouse brain
title_short Microarray analysis of gene expression in the diacylglycerol kinase η knockout mouse brain
title_sort microarray analysis of gene expression in the diacylglycerol kinase η knockout mouse brain
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597918/
https://www.ncbi.nlm.nih.gov/pubmed/31297456
http://dx.doi.org/10.1016/j.bbrep.2019.100660
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