• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Pathophysiological mechanisms for microcephaly and macrocephaly

Research Project

Project/Area Number 18K06504
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 46020:Anatomy and histopathology of nervous system-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Hikaru Ito  東京医科歯科大学, 統合研究機構, 助教 (50587392)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords神経発達障害 / 小頭症 / 発生 / モデル動物 / 神経科学 / 発達障害 / 分化
Outline of Final Research Achievements

There are no therapeutic methods for microcephaly and macrocephaly. Moreover, pathophysiological mechanisms underlying these neurodevelopmental disorders remain unclear. Therefore, we had tried to generate novel kdm5c mutant cell and mouse models by using CRISPR-Cas9 system for developing models of microcephaly and macrocephaly.
At first, we developed the cell models. And, we also analysed the gene expression levels in the cells and brains of Kdm5c mutant mice which has been showed microcephaly. As a results, we found that some genes of the neural differentiation category were up-regulated in the cells and brains of Kdm5c mutant mice. And also, we found novel KDM5c binding protein which has been thought as a regulator of neural differentiation.

Academic Significance and Societal Importance of the Research Achievements

本課題の研究成果によって、小頭症を引き起こす新たなメカニズムの一端を解明できる可能性が示唆された。小頭症の病態メカニズムは未だ不明な点が多く、今後、さらに精査していくことにより、将来的な小頭症の治療へと応用することも十分可能であると考えている。さらには、本研究成果を発端として小頭症だけでなく大頭症など脳の大きさに異常をきたす神経発達障害の根本的な治療法開発へとつなげていく。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2020 2019 Other

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (2 results) Remarks (3 results)

  • [Journal Article] Activation of proprotein convertase in the mouse habenula causes depressive-like behaviors through remodeling of extracellular matrix2020

    • Author(s)
      Ito Hikaru、Nozaki Kanako、Sakimura Kenji、Abe Manabu、Yamawaki Shigeto、Aizawa Hidenori
    • Journal Title

      Neuropsychopharmacology

      Volume: 46 Issue: 2 Pages: 442-454

    • DOI

      10.1038/s41386-020-00843-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dopaminergic signaling in the nucleus accumbens modulates stress-coping strategies during inescapable stress.2020

    • Author(s)
      Cui, W., Aida, T., Ito, H., Kobayashi, K., Wada, Y., Kato, S., Nakano, T., Zhu, M., Isa, K., Kobayashi, K., Isa, T., Tanaka, K. and Aizawa, H.
    • Journal Title

      J Neurosci.

      Volume: 40 Issue: 38 Pages: 7241-7254

    • DOI

      10.1523/jneurosci.0444-20.2020

    • NAID

      120007170786

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Antidepressant effect of the translocator protein antagonist ONO-2952 on mouse behaviors under chronic social defeat stress2020

    • Author(s)
      Nozaki Kanako、Ito Hikaru、Ohgidani Masahiro、Yamawaki Yosuke、Sahin Ezgi Hatice、Kitajima Takashi、Katsumata Seishi、Yamawaki Shigeto、Kato Takahiro A.、Aizawa Hidenori
    • Journal Title

      Neuropharmacology

      Volume: 162 Pages: 107835-107835

    • DOI

      10.1016/j.neuropharm.2019.107835

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phospholipase C-related catalytically inactive protein regulates lipopolysaccharide-induced hypothalamic inflammation-mediated anorexia in mice2019

    • Author(s)
      Yamawaki Yosuke、Shirawachi Satomi、Mizokami Akiko、Nozaki Kanako、Ito Hikaru、Asano Satoshi、Oue Kana、Aizawa Hidenori、Yamawaki Shigeto、Hirata Masato、Kanematsu Takashi
    • Journal Title

      Neurochemistry International

      Volume: 131 Pages: 104563-104563

    • DOI

      10.1016/j.neuint.2019.104563

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 細胞外基質分解酵素の不活性化によるうつ病モデルマウスの治療2020

    • Author(s)
      伊藤日加瑠、野崎香菜子、相澤秀紀
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Generation of myogenic stem cells from iPS cells via blastocyst complementation.2019

    • Author(s)
      伊藤日加瑠
    • Organizer
      第66回日本実験動物学会総会
    • Related Report
      2019 Research-status Report
  • [Remarks] 【研究成果】脳深部の炎症を引き起こすうつ病関連遺伝子PCSK5を発見

    • URL

      https://www.hiroshima-u.ac.jp/news/60145

    • Related Report
      2020 Annual Research Report
  • [Remarks] うつ病様異常に関与する新規遺伝子を発見

    • URL

      https://neurobio.hiroshima-u.ac.jp/ja/post/20200918/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 伊藤日加瑠助教の筆頭著者の論文がOnline版で掲載されました

    • URL

      http://www.tmd-cea.jp/eam/topics/1276

    • Related Report
      2020 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi