Regulation of retrotransposable elements in the mammalian neuron by Interleukin family members
| Project/Area Number |
19K22368
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 42:Veterinary medical science, animal science, and related fields
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| Research Institution | Hiroshima University (2020)
Kyushu University (2019) |
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Principal Investigator |
Imamura Takuya 広島大学, 統合生命科学研究科(理), 教授 (90390682)
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| Project Period (FY) |
2019-06-28 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
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| Keywords | レトロトランスポゾン / インターロイキン / IL17D |
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| Outline of Research at the Start |
慢性炎症では、例え細胞死を逃れたとしても、ゲノムに内在するレトロトランスポゾン等のウイルス由来転移因子の持続的活性化が引き起こされてしまう。申請者は慢性炎症から神経細胞のゲノムを根本的に守る方法論の開発を発想し、最近、神経細胞自身が産生するインターロイキン系液性因子であるIL17Dがこのリスクに対処しうることを見出した。本研究では、単純な液性因子投与による慢性疾患の防止機構を解明し、動物病態制御の簡便化に繋げていく。
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| Outline of Final Research Achievements |
Maternal immune activation (MIA) promotes the abnormal cortical formation that causes the incidence of autism spectrum disorder in offspring. IL-17 cytokine family members, especially Interleukin-17A (IL-17A) produced by Th17 cells, have been believed to mediate this phenomenon through NF-kB pathway. We find unexpected pattern of interleukin-17D (IL-17D) expression in neural stem/precursor cells. It increases during mouse brain development, raising the possibility that IL-17D has a supportive function differently from IL-17A. Functional studies indicated that apoptotic cells increased after Il17d knockdown and exogenous IL-17D can protect from MIA-induced abnormal cortical formation in the fetal brain through MEK pathway. Our data suggest that neural IL-17D supports normal brain development in offspring to resist against maternally derived inflammatory IL-17A signals.
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| Academic Significance and Societal Importance of the Research Achievements |
今回、マウスを活用した研究により、医療や動物生産に向けたインターロイキン類の新しい利用法が提案できた。妊娠時の胎児の健康管理は緊喫の課題であり、全ての脳細胞の根幹をなすゲノムについて、その崩壊を末梢投与により簡便に食い止めることができる可能性が出てきたことにより、今後は、IL17Dを含むインターロイキン類の制御により母体の免疫を管理することで、出生児の統合失調症発症リスクを根本から抑える方法論の開発が期待できる。
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Report
(3 results)
Research Products
(22 results)
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[Journal Article] MeCP2 controls neural stem cell fate specification through miR-199a-mediated inhibition of BMP-Smad signaling2021
Author(s)
Nakashima H, Tsujimura K, Irie K, Imamura T, Trujillo CA, Ishizu M, Uesaka K, Pan M, Noguchi H, Andoh-Noda T, Okano H, Muotri AR, Nakashima K
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Journal Title
Cell Rep
Volume: in press
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Conditional Kisspeptin Neuron-Specific Kiss1 Knockout With Newly Generated Kiss1-floxed and Kiss1-Cre Mice Replicates a Hypogonadal Phenotype of Global Kiss1 Knockout Mice2020
Author(s)
Kana Ikegami, Teppei Goto, Sho Nakamura, Youki Watanabe, Arisa Sugimoto, Sutisa Majarune, Kei Horihata, Mayuko Nagae, Junko Tomikawa, Takuya Imamura, Makoto Sanbo, Masumi Hirabayashi, Naoko Inoue, Kei-Ichiro Maeda, Hiroko Tsukamura, Yoshihisa Uenoyama
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Journal Title
J Reprod Dev.
Volume: in press
Issue: 4
Pages: 359-367
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inducible Kiss1 knockdown in the hypothalamic arcuate nucleus suppressed pulsatile secretion of luteinizing hormone in male mice2020
Author(s)
Shiori Minabe, Sho Nakamura, Eri Fukushima, Marimo Sato, Kana Ikegami, Teppei Goto, Makoto Sanbo, Masumi Hirabayashi, Junko Tomikawa, Takuya Imamura, Naoko Inoue, Yoshihisa Uenoyama, Hiroko Tsukamura, Kei-Ichiro Maeda, Fuko Matsuda
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Journal Title
Journal of Reproduction and Development
Volume: Epub
Issue: 4
Pages: 369-375
DOI
NAID
Related Report
Peer Reviewed / Open Access
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