Development of epigenetic drugs for neurodevelopmental disorders
Project/Area Number |
15K09592
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Pediatrics
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Research Institution | University of Yamanashi |
Principal Investigator |
MIYAKE Kunio 山梨大学, 大学院総合研究部, 准教授 (60550712)
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | エピジェネティクス / 抗精神病薬 / ヒストン修飾 / 神経変性疾患 / 神経細胞死 / 発達障害 / 精神疾患 / ヒストン脱アセチル化 / レット症候群 / iPS細胞 / BDNF |
Outline of Final Research Achievements |
Antidepressants are known to alter gene expression patterns by inducing changes in the epigenetic status of neuronal cells. We examined whether antidepressants exert an anti-apoptotic effect via epigenetic mechanisms. We analyzed global gene expression in mouse primary cortical neurons after treatment with antidepressants. The neuroprotection-associated genes, activating transcription factor 3 (Atf3) and heme oxygenase 1 (Hmox1), were up-regulated by treatment with amitriptyline. Quantitative chromatin immunoprecipitation assay revealed that amitriptyline increased enrichments of trimethylation of histone H3 lysine 4 in the promoter regions of Atf3 and Hmox1, which indicate an active epigenetic status. Amitriptyline pre-treatment attenuated 1-methyl-4-phenylpyridinium ion- or amyloid beta 1-42-induced neuronal cell death and inhibited the activation of extracellular signal-regulated kinase 1 and 2. These findings suggest preconditioning and neuroprotective effects of amitriptyline.
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Protein-restricted diet during pregnancy after insemination alters behavioral phenotypes of the progeny2017
Author(s)
Furuse T, Miyake K, Kohda T, Kaneda H, Hirasawa T, Yamada I, Kushida T, Kashimura M, Kobayashi K, Ishino F, Kubota T, Wakana S.
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Journal Title
Genes & Nutrition
Volume: 12
Issue: 1
Pages: 1-1
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A Female Patient with Incomplete Hemophagocytic Lymphohistiocytosis Caused by a Heterozygous XIAP Mutation Associated with Non-Random X-Chromosome Inactivation Skewed Towards the Wild-Type XIAP Allele2015
Author(s)
Yang X, Hoshino A, Taga T, Kunitsu T, Ikeda Y, Yasumi T, Yoshida K, Wada T, Miyake K, Kubota T, Okuno Y, Muramatsu H, Adachi Y, Miyano S, Ogawa S, Kojima S, Kanegane H
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Journal Title
J Clin Immunol
Volume: 35(3)
Issue: 3
Pages: 244-8
DOI
Related Report
Peer Reviewed
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[Journal Article] Differentiation of multipotent neural stem cells derived from Rett syndrome patients is biased toward the astrocytic lineage2015
Author(s)
Andoh-Noda T, Akamatsu W, Miyake K, Matsumoto T, Yamaguchi R, Sanosaka T, Okada Y, Kobayashi T, Ohyama M, Nakashima K, Kurosawa H, Kubota T, Okano H
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Journal Title
Mol Brain
Volume: 8
Issue: 1
Pages: 31-31
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Involvement of Allele-Specific Methylation of Asparagine Synthetase Gene is in Asparaginase Sensitivity of BCP-ALL2016
Author(s)
Atsushi Watanabe, Takeshi Inukai, Minori Tamai, Tamao Shinohara, Shinpei Somazu, Hiroko Oshiro, Koushi Akahane, Kumiko Goi, Kunio Miyake, Kevin Y Urayama, Kanji Sugita.
Organizer
58th American Society of Hematology Annual meating
Place of Presentation
San Diego(USA)
Year and Date
2016-12-03
Related Report
Int'l Joint Research
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[Presentation] Association of BIM gene silencing by hypermethylation with chemoresistance in BCP-ALL.2016
Author(s)
Meixian Huang, Takeshi Inukai, Kunio Miyake, Keiko Kagami, Masako Abe, Tamao Shinohara, Atsushi Watanabe, Shinpei Somazu, Hiroko Oshiro, Kumiko Goi, Kanji Sugita.
Organizer
第78回日本血液学会
Place of Presentation
パシフィコ横浜(神奈川県・横浜市)
Year and Date
2016-10-13
Related Report
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