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Molecular analysis of the effects of environmental factors on higher brain function using iPSC technology and mice

Research Project

Project/Area Number 22K18655
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 10:Psychology and related fields
Research InstitutionTokyo University of Agriculture

Principal Investigator

Nakazawa Takanobu  東京農業大学, 生命科学部, 教授 (00447335)

Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords3q29領域欠失 / 疾患モデルマウス / ultrasonic vocalization / 環境エンリッチメント / 環境要因 / 自閉スペクトラム症 / iPS細胞技術
Outline of Research at the Start

自閉スペクトラム症(自閉症)の病因や病態の分子メカニズムは不明な点が多く残されています。近年、環境要因が自閉症と関連している可能性が注目されていますが、環境要因が脳機能に影響を与える分子メカニズムはほとんど不明です。本研究では、iPS細胞とヒト型疾患モデルマウスを用いて、不明な点が多い環境エンリッチメントといった環境要因を分子レベルで記述し、自閉症の分子病態の一端を明らかにすることをめざします。

Outline of Final Research Achievements

The mechanism of onset for autism spectrum disorder remains largely unknown. In this study, we are focusing on environmental factors using a disease-model mouse with high validity for autism spectrum disorder. Specifically, we found that enriching the breeding environment of mother mice resulted in the recovery of social behavioral abnormalities and developmental abnormalities in the nervous system of neonatal disease model mice. Taken Together, we provided data that contributes to understanding the molecular and cellular pathogenesis of autism spectrum disorder and molecular mechanism behind environmental factors, as well as therapeutic interventions for autism spectrum disorder.

Academic Significance and Societal Importance of the Research Achievements

本研究により、環境要因というファクターが脳機能、特に社会性行動の制御機構や脳発達に与える影響の一端が分子レベルで明らかになりました。本研究成果から、自閉スペクトラム症の分子病態のみならず、環境要因に関する分子レベルの理解、及び自閉スペクトラム症の創薬に貢献する基礎データを提供することができたと考えられます。本研究成果は、社会的急務の自閉スペクトラム症の解決を加速することが期待される点で学術的意義が大きいものです。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (16 results)

All 2024 2023 2022

All Journal Article (9 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 9 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 5 results)

  • [Journal Article] Clozapine Induces Neuronal Activation in the Medial Prefrontal Cortex in a Projection Target-Biased Manner2024

    • Author(s)
      Yumi Hirato, Kaoru Seiriki, Leo Kojima, Shohei Yamada, Hiroki Rokujo, Tomoya Takemoto, Takanobu Nakazawa, Atsushi Kasai, Hitoshi Hashimoto
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 47 Issue: 2 Pages: 478-485

    • DOI

      10.1248/bpb.b23-00898

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2024-02-22
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-lasting anti-despair and anti-anhedonia effects of (S)-norketamine in social isolation-reared mice2024

    • Author(s)
      Yokoyama Rei、Higuchi Momoko、Tanabe Wataru、Tsukada Shinji、Igarashi Hisato、Seiriki Kaoru、Nakazawa Takanobu、Kasai Atsushi、Ago Yukio、Hashimoto Hitoshi
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 154 Issue: 2 Pages: 72-76

    • DOI

      10.1016/j.jphs.2023.12.005

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] (R)-ketamine restores anterior insular cortex activity and cognitive deficits in social isolation-reared mice2024

    • Author(s)
      Yokoyama Rei、Ago Yukio、Igarashi Hisato、Higuchi Momoko、Tanuma Masato、Shimazaki Yuto、Kawai Takafumi、Seiriki Kaoru、Hayashida Misuzu、Yamaguchi Shun、Tanaka Hirokazu、Nakazawa Takanobu、Okamura Yasushi、Hashimoto Kenji、Kasai Atsushi、Hashimoto Hitoshi
    • Journal Title

      Molecular Psychiatry

      Volume: - Issue: 5 Pages: 1-11

    • DOI

      10.1038/s41380-024-02419-6

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blockade of vasoactive intestinal peptide receptor 2 (VIPR2) signaling suppresses cyclin D1-dependent cell-cycle progression in MCF-7 cells2024

    • Author(s)
      Asano Satoshi、Ono Ami、Baba Kaede、Uehara Teru、Sakamoto Kotaro、Hayata-Takano Atsuko、Nakazawa Takanobu、Yanamoto Souichi、Tanimoto Kotaro、Hashimoto Hitoshi、Ago Yukio
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 154 Issue: 3 Pages: 139-147

    • DOI

      10.1016/j.jphs.2024.01.002

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phenotypes for general behavior, activity, and body temperature in 3q29 deletion model mice2024

    • Author(s)
      Mori D、Ikeda R、Sawahata M、Yamaguchi S、Kodama A、Hirao T、Arioka Y、Okumura H、Inami C、Suzuki T、Hayashi Y、Kato H、Nawa Y、Miyata S、Kimura H、Kushima I、Aleksic B、Mizoguchi H、Nagai T、Nakazawa T、Hashimoto R、Kaibuchi K、Kume K、Yamada K、Ozaki N
    • Journal Title

      Translational Psychiatry

      Volume: 14 Issue: 1 Pages: 138-138

    • DOI

      10.1038/s41398-023-02679-w

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modeling mental disorders in a dish2023

    • Author(s)
      Nakazawa Takanobu
    • Journal Title

      Psychiatry and Clinical Neurosciences

      Volume: 77 Issue: 6 Pages: 307-307

    • DOI

      10.1111/pcn.13552

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dorsal raphe serotonergic neurons preferentially reactivate dorsal dentate gyrus cell ensembles associated with positive experience2023

    • Author(s)
      Nagai Yuma、Kisaka Yuri、Nomura Kento、Nishitani Naoya、Andoh Chihiro、Koda Masashi、Kawai Hiroyuki、Seiriki Kaoru、Nagayasu Kazuki、Kasai Atsushi、Shirakawa Hisashi、Nakazawa Takanobu、Hashimoto Hitoshi、Kaneko Shuji
    • Journal Title

      Cell Reports

      Volume: 42 Issue: 3 Pages: 112149-112149

    • DOI

      10.1016/j.celrep.2023.112149

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vasoactive intestinal peptide receptor 2 signaling promotes breast cancer cell proliferation by enhancing the ERK pathway2023

    • Author(s)
      Asano Satoshi、Ono Ami、Sakamoto Kotaro、Hayata-Takano Atsuko、Nakazawa Takanobu、Tanimoto Kotaro、Hashimoto Hitoshi、Ago Yukio
    • Journal Title

      Peptides

      Volume: 161 Pages: 170940-170940

    • DOI

      10.1016/j.peptides.2023.170940

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vasoactive intestinal peptide?VIPR2 signaling regulates tumor cell migration2022

    • Author(s)
      Asano Satoshi、Yamasaka Misa、Ozasa Kairi、Sakamoto Kotaro、Hayata-Takano Atsuko、Nakazawa Takanobu、Hashimoto Hitoshi、Waschek James A.、Ago Yukio
    • Journal Title

      Frontiers in Oncology

      Volume: 12 Pages: 852358-852358

    • DOI

      10.3389/fonc.2022.852358

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Basic and clinical collaborative research on psychiatric disorders2023

    • Author(s)
      Takanobu Nakazawa, Hitoshi Hashimoto, Ryota Hashimoto
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Modeling psychiatric disorders with iPS cell technology and disease mouse models2023

    • Author(s)
      Takanobu Nakazawa
    • Organizer
      The 2nd RIKEN CBS Co-Creation International Conference
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] iPS細胞技術を用いた精神疾患のリバーストランスレーショナルリサーチ2023

    • Author(s)
      中澤敬信
    • Organizer
      第97回日本薬理学会年会・第44回日本臨床薬理学会学術総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] iPS細胞技術及び疾患モデルマウスを用いた発達障害に関わる分子病態研究2023

    • Author(s)
      中澤敬信
    • Organizer
      遺伝研研究会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 妊娠期の環境エンリッチメントが脳機能に与える影響の分子メカニズム解析2023

    • Author(s)
      奥山灯、秋本祐弥、福島穂高、三浦大樹、中澤敬信
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Research-status Report
  • [Presentation] 環境エンリッチメントによる3q29領域欠失導入マウスの精神疾患様行動の回復2023

    • Author(s)
      秋本祐弥、馬場優志、福島穂高、三浦大樹、橋本均、橋本亮太、中澤敬信
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Research-status Report
  • [Presentation] Modelling psychiatric disorders with patient iPSC-derived neurons and mouse disease models2022

    • Author(s)
      Nakazawa T
    • Organizer
      Molecular and Cellular Cognition Society Asia
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2022-07-05   Modified: 2025-01-30  

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