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Molecular mechanism for brain development and aging

Research Project

Project/Area Number 18H02537
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 46020:Anatomy and histopathology of nervous system-related
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

OKADO Haruo  公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 研究員 (60221842)

Co-Investigator(Kenkyū-buntansha) 平井 志伸  公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 主任研究員 (00625189)
田中 智子  公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 研究員 (40578986)
新保 裕子  地方独立行政法人神奈川県立病院機構神奈川県立こども医療センター(臨床研究所), 臨床研究所, 研究員 (50724663)
三輪 秀樹  国立研究開発法人国立精神・神経医療研究センター, 精神保健研究所 精神薬理研究部, 室長 (80468488)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
KeywordsRP58 / 老化 / 認知機能 / 転写抑制因子 / DNA修復 / 認知機能異常 / 高次脳機能 / グルタミン酸ニューロン
Outline of Final Research Achievements

Analysis of the RP58 heterozygous mouse revealed that this mouse could be a model mouse for RP58 haploinsufficiency. Detailed analysis revealed behavioral abnormalities such as impaired cognitive function, reversal learning ability, and cerebellar learning ability, as well as posterior corpus callosum defects, reduced glutamine receptor expression, and maturation failure of the mature spine. In addition, an object location recognition test and hippocampal tissue analysis revealed findings of early aging, indicating that the mice could be used as a model for early brain aging.

Academic Significance and Societal Importance of the Research Achievements

RP58ハプロ不全のモデルマウスを確立したことで、治療法の開発に役立つ可能性が見出された。すなわち、RP58の発現量の不足が認知機能低下を引き起こすことが実証され、その原因として、興奮性ニューロンの興奮性シナプスのスパイン成熟不全であることが示唆された。このことは、RP58ハプロ不全の認知機能障害の予防法、治療法の開発の糸口になると期待される。また、知的障害が老化の側面を有することが明らかになり、知的障害と老化研究が、相互連環を持ちながら研究できる基礎となることが期待できる。

Report

(5 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (12 results)

All 2023 2021 2019 2018

All Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 9 results,  Open Access: 6 results) Presentation (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Serotonergic neurons control cortical neuronal intracellular energy dynamics by modulating astrocyte-neuron lactate shuttle2023

    • Author(s)
      Natsubori Akiyo、Hirai Shinobu、Kwon Soojin、Ono Daisuke、Deng Fei、Wan Jinxia、Miyazawa Momoka、Kojima Takashi、Okado Haruo、Karashima Akihiro、Li Yulong、Tanaka Kenji F.、Honda Makoto
    • Journal Title

      iScience

      Volume: 26 Issue: 1 Pages: 105830-105830

    • DOI

      10.1016/j.isci.2022.105830

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] GAD67-mediated GABA Synthesis and Signaling Impinges on Directing Basket Cell Axonal Projections Toward Purkinje Cells in the Cerebellum2021

    • Author(s)
      Miwa Hideki、Kobayashi Ken、Hirai Shinobu、Yamada Mitsuhiko、Watanabe Masahiko、Okado Haruo、Yanagawa Yuchio
    • Journal Title

      The Cerebellum

      Volume: Published: 21 October 2021 Issue: 6 Pages: 1-15

    • DOI

      10.1007/s12311-021-01334-8

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High-sucrose diets contribute to brain angiopathy with impaired glucose uptake and psychosis-related higher brain dysfunctions in mice2021

    • Author(s)
      Hirai Shinobu, Toriumi Kazuya (4番目/24人中), et al.
    • Journal Title

      Science Advances

      Volume: 7 Issue: 46 Pages: 1-5

    • DOI

      10.1126/sciadv.abl6077

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Early-life stress induces the development of Alzheimer's disease pathology via angiopathy2021

    • Author(s)
      Tanaka Tomoko、Hirai Shinobu、Hosokawa Masato、Saito Takashi、Sakuma Hiroshi、Saido Takaomi、Hasegawa Masato、Okado Haruo
    • Journal Title

      Experimental Neurology

      Volume: 337 Pages: 113552-113552

    • DOI

      10.1016/j.expneurol.2020.113552

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Nervous system regulated by POZ domain Kruppel-like zinc finger (POK) family transcription repressor RP582021

    • Author(s)
      Haruo Okado
    • Journal Title

      Br J Pharmacol.

      Volume: 178 Issue: 4 Pages: 813-826

    • DOI

      10.1111/bph.15265

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of brain development and brain function by the transcriptional repressor RP58.2019

    • Author(s)
      Okado H
    • Journal Title

      Brain Research

      Volume: 1795 Pages: 15-23

    • DOI

      10.1016/j.brainres.2018.02.042

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Corticobasal ganglia projecting neurons are required for juvenile vocal learning but not for adult vocal plasticity in songbirds2019

    • Author(s)
      Sanchez-Valpuesta M, Suzuki Y, Shibata Y, Toji N, Ji Y, Afrin N, Asogwa CN, Kojima I, Mizuguchi D, Kojima S, Okanoya K, Okado H, Kobayashi K, Wada K
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 116 Issue: 45 Pages: 22833

    • DOI

      10.1073/pnas.1913575116

    • NAID

      120006842193

    • URL

      https://localhost/en/publications/c967dcf5-86fd-4ece-bcf9-3ac1ae1f9385

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Zfp238 Regulates the Thermogenic Program in Cooperation with Foxo1.2019

    • Author(s)
      Kita M, Nakae J, Kawano Y, Asahara H, Takemori H, Okado H, Itoh H
    • Journal Title

      iScience

      Volume: 12 Pages: 87-101

    • DOI

      10.1016/j.isci.2019.01.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Developmental Roles and Evolutionary Significance of AMPA-Type Glutamate Receptors.2018

    • Author(s)
      Hirai S, Hotta K, Okado H.
    • Journal Title

      BioEssays

      Volume: 40 Issue: 9 Pages: 1800028-1800028

    • DOI

      10.1002/bies.201800028

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Mechanism for the maintenance of cognitive function, Neuro20192019

    • Author(s)
      Tomoko Tanaka, Okado Haruo.
    • Organizer
      第42回日本神経科学大会 July 25-28 Niigata
    • Related Report
      2019 Annual Research Report
  • [Presentation] 成体でのRP58発現抑制は認知機能低下を惹起する2019

    • Author(s)
      新保 裕子、平井 志伸、田中 智子、田中 謙二、岡戸 晴生
    • Organizer
      第42回日本神経科学大会 July 25-28 Niigata
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 転写抑制因子RP58の発現制御可能なトランスジェニック非ヒト動物2019

    • Inventor(s)
      岡戸晴生、新保裕子
    • Industrial Property Rights Holder
      公益財団法人東京都医学総合研究所
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2024-01-30  

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