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Identification and characterization of brain disorder-related singularity cells by whole-brain imaging

Planned Research

Project AreaSingularity biology
Project/Area Number 18H05416
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Complex systems
Research InstitutionOsaka University

Principal Investigator

Hashimoto Hitoshi  大阪大学, 大学院薬学研究科, 教授 (30240849)

Co-Investigator(Kenkyū-buntansha) 中澤 敬信  東京農業大学, 生命科学部, 教授 (00447335)
Project Period (FY) 2018-06-29 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥128,960,000 (Direct Cost: ¥99,200,000、Indirect Cost: ¥29,760,000)
Fiscal Year 2022: ¥25,870,000 (Direct Cost: ¥19,900,000、Indirect Cost: ¥5,970,000)
Fiscal Year 2021: ¥26,910,000 (Direct Cost: ¥20,700,000、Indirect Cost: ¥6,210,000)
Fiscal Year 2020: ¥25,480,000 (Direct Cost: ¥19,600,000、Indirect Cost: ¥5,880,000)
Fiscal Year 2019: ¥24,050,000 (Direct Cost: ¥18,500,000、Indirect Cost: ¥5,550,000)
Fiscal Year 2018: ¥26,650,000 (Direct Cost: ¥20,500,000、Indirect Cost: ¥6,150,000)
Keywordsシンギュラリティ細胞 / 自閉スペクトラム症 / ストレス / シンギュラリティ / 脳疾患 / iPS / シンギュラリティ現象 / 高精細組織全細胞イメージング / ビッグデータ解析 / 精神疾患 / 全脳 / イメージング
Outline of Final Research Achievements

The aim of this study was to elucidate the singularity phenomenon in brain disorders, such as mental illnesses, which occur when the activity of a specific subset of brain cells explosively spreads to a wide brain region, leading to widespread changes in neuronal activity. We developed methodologies to comprehensively observe and analyze a vast number of brain cells, as well as neuronal activation reporter systems and foundational technologies related to induced pluripotent stem cells. Furthermore, we revealed the significance of abnormal activity in an exceedingly small number of neurons within the brains in stress-exposed mice and a mouse model of autism spectrum disorder, as it relates to the expression of behavioral abnormalities.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、創薬の標的としての脳疾患におけるシンギュラリティ現象の同定が可能になったことである。精神疾患分野では、新規分子病態を標的とする創薬が難航しており、既存薬の治療効果も限定的である。本研究の実施により創薬につながる新しい分子病態情報を得ることができ、急務である中枢神経系創薬の推進に貢献することが期待される点で、本研究は社会的要求が著しく高いといえる。

Report

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

    (21 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (14 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 14 results,  Open Access: 14 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Remarks (1 results)

  • [Int'l Joint Research] UCLA(米国)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Molecular basis of astrocyte diversity and morphology across the CNS in health and disease2022

    • Author(s)
      Endo F, Kasai A, Soto JS, Yu X, Qu Z, Hashimoto H, Gradinaru V, Kawaguchi R, Khakh BS.
    • Journal Title

      Science

      Volume: 378 Issue: 6619

    • DOI

      10.1126/science.adc9020

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Claustrum mediates bidirectional and reversible control of stress-induced anxiety responses2022

    • Author(s)
      Niu M et al.
    • Journal Title

      Science Advances

      Volume: 8

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autism-associated ANK2 regulates embryonic neurodevelopment2022

    • Author(s)
      Kawano Shotaro、Baba Masayuki、Fukushima Hotaka、Miura Daiki、Hashimoto Hitoshi、Nakazawa Takanobu
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 605 Pages: 45-50

    • DOI

      10.1016/j.bbrc.2022.03.058

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oxytocin ameliorates impaired social behavior in a mouse model of 3q29 deletion syndrome2022

    • Author(s)
      Takemoto Tomoya、Baba Masayuki、Yokoyama Kazumasa、Kitagawa Kohei、Nagayasu Kazuki、Ago Yukio、Seiriki Kaoru、Hayata-Takano Atsuko、Kasai Atsushi、Mori Daisuke、Ozaki Norio、Takuma Kazuhiro、Hashimoto Ryota、Hashimoto Hitoshi、Nakazawa Takanobu
    • Journal Title

      Molecular Brain

      Volume: 15 Issue: 1 Pages: 26-26

    • DOI

      10.1186/s13041-022-00915-w

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Altered Functional Connectivity of the Orbital Cortex and Striatum Associated with Catalepsy Induced by Dopamine D1 and D2 Antagonists2021

    • Author(s)
      Misaki Niu, Atsushi Kasai, Kaoru Seiriki, Misuzu Hayashida, Masato Tanuma, Rei Yokoyama, Yumi Hirato, Hitoshi Hashimoto
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 44 Issue: 3 Pages: 442-447

    • DOI

      10.1248/bpb.b20-01006

    • NAID

      130007993460

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2021-03-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiple alterations in glutamatergic transmission and dopamine D2 receptor splicing in induced pluripotent stem cell-derived neurons from patients with familial schizophrenia2021

    • Author(s)
      Yamamoto Kana、Kuriu Toshihiko、Takuma Kazuhiro、Ono Fumihito、Matsumoto Naomichi、Hashimoto Ryota、Hashimoto Hitoshi、Nakazawa Takanobu
    • Journal Title

      Translational Psychiatry

      Volume: 11 Issue: 1 Pages: 548-548

    • DOI

      10.1038/s41398-021-01676-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PACAP-PAC1 Signaling Regulates Serotonin 2A Receptor Internalization2021

    • Author(s)
      Hayata-Takano A et al.
    • Journal Title

      Frontiers in Endocrinology

      Volume: 12 Pages: 732456-732456

    • DOI

      10.3389/fendo.2021.732456

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intranasal oxytocin administration ameliorates social behavioral deficits in a POGZWT/Q1038R mouse model of autism spectrum disorder2021

    • Author(s)
      Kitagawa Kohei、Matsumura Kensuke、Baba Masayuki、Kondo Momoka、Takemoto Tomoya、Nagayasu Kazuki、Ago Yukio、Seiriki Kaoru、Hayata-Takano Atsuko、Kasai Atsushi、Takuma Kazuhiro、Hashimoto Ryota、Hashimoto Hitoshi、Nakazawa Takanobu
    • Journal Title

      Molecular Brain

      Volume: 14 Issue: 1 Pages: 56-56

    • DOI

      10.1186/s13041-021-00769-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lipocalin-type prostaglandin D synthase regulates light-induced phase advance of the central circadian rhythm in mice2020

    • Author(s)
      Kawaguchi, C., Shintani, N., Hayata-Takano, A., Hatanaka, M., Kuromi, A., Nakamura, R., Yamano, Y., Shintani, Y., Nagai, K., Tsuchiya, S., Sugimoto, Y., Ichikawa, A., Okuno, Y., Urade, Y., Hirai, H., Nagata, K., Nakamura, M., Narumiya, S., Nakazawa, T., Kasai, A., Ago, Y., Takuma, K., Baba, A., and Hashimoto, H.
    • Journal Title

      Communications Biology

      Volume: 3 Issue: 1 Pages: 557-557

    • DOI

      10.1038/s42003-020-01281-w

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation of the VPAC2 Receptor Impairs Axon Outgrowth and Decreases Dendritic Arborization in Mouse Cortical Neurons by a PKA-Dependent Mechanism2020

    • Author(s)
      Takeuchi Shuto、Kawanai Takuya、Yamauchi Ryosuke、Chen Lu、Miyaoka Tatsunori、Yamada Mei、Asano Satoshi、Hayata-Takano Atsuko、Nakazawa Takanobu、Yano Koji、Horiguchi Naotaka、Nakagawa Shinsaku、Takuma Kazuhiro、Waschek James A.、Hashimoto Hitoshi、Ago Yukio
    • Journal Title

      Frontiers in Neuroscience

      Volume: 14 Pages: 521-532

    • DOI

      10.3389/fnins.2020.00521

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes.2020

    • Author(s)
      Matsumura K, (33名中略), Hashimoto R, (37名中35番目),Hashimoto H, Nakazawa T.
    • Journal Title

      Nat. Commun

      Volume: 11(1) Issue: 1 Pages: 859-859

    • DOI

      10.1038/s41467-020-14697-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Direct visualization of an antidepressant analog using surface-enhanced Raman scattering in the brain2020

    • Author(s)
      Masato Tanuma, Atsushi Kasai, Kazuki Bando, Naoyuki Kotoku, Kazuo Harada, Masafumi Minoshima, Kosuke Higashino, Atsushi Kimishima, Masayoshi Arai, Yukio Ago, Kaoru Seiriki, Kazuya Kikuchi, Satoshi Kawata, Katsumasa Fujita, Hitoshi Hashimoto
    • Journal Title

      JCI Insight

      Volume: 5 Issue: 6

    • DOI

      10.1172/jci.insight.133348

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autism-associated protein kinase D2 regulates embryonic cortical neuron development.2019

    • Author(s)
      Matsumura K, Baba M, Nagayasu K, Yamamoto K, Kondo M, Kitagawa K, Takemoto T, Seiriki K, Kasai A, Ago Y, Hayata-Takano A, Shintani N, Kuriu T, Iguchi T, Sato M, Takuma K, Hashimoto R, Hashimoto H.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 519(3) Issue: 3 Pages: 626-632

    • DOI

      10.1016/j.bbrc.2019.09.048

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] mS-11, a mimetic of the mSin3-binding helix in NRSF, ameliorates social interaction deficits in a prenatal valproic acid-induced autism mouse model.2019

    • Author(s)
      Kawase H, Ago Y, Naito M, Higuchi M, Hara Y, Hasebe S, Tsukada S, Kasai A, Nakazawa T, Mishina T, Kouji H, Takuma K, Hashimoto H.
    • Journal Title

      Pharmacol Biochem Behav.

      Volume: 176 Pages: 1-5

    • DOI

      10.1016/j.pbb.2018.11.003

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 脳疾患の病態解析と創薬へ向けたアンバイアス全脳イメージング2019

    • Author(s)
      橋本均
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] High-speed and scalable whole-brain imaging system FAST2018

    • Author(s)
      橋本均
    • Organizer
      第56回日本生物物理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] High-speed and high-resolution whole-brain imaging system FAST (block-face serial microscopy tomography)2018

    • Author(s)
      Hitoshi Hashimoto, Kaoru Seiriki, Atsushi Kasai, Takanobu Nakazawa
    • Organizer
      Cold Spring Harbor Asia, Advances in Optical Imaging of Living Cells & Organisms: Focus on the Brain
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Whole-brain analysis of the NMDA receptor antagonist-induced neuronal activation in mice using high-speed and high-resolution imaging system FAST (block-face serial microscopy tomography)2018

    • Author(s)
      Kaoru Seiriki, Atsushi Kasai, Takanobu Nakazawa, Hitoshi Hashimoto
    • Organizer
      Cold Spring Harbor Asia, Advances in Optical Imaging of Living Cells & Organisms: Focus on the Brain
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] iPS細胞関連技術とヒト型疾患モデルマウスを用いた精神疾患の分子病態解析2018

    • Author(s)
      中澤敬信、橋本亮太、田熊一敞、橋本均
    • Organizer
      第48回日本神経精神薬理学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Remarks] 大阪大学大学院薬学研究科神経薬理学分野ホームページ

    • URL

      http://molpharm.umin.jp/

    • Related Report
      2018 Annual Research Report

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Published: 2018-07-20   Modified: 2024-01-30  

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