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Analysis of pathological mechanism of cognitive impairment and neurodevelopmental disorder observed in the new model mouse of extremely preterm infants

Research Project

Project/Area Number 18K07855
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionKeio University

Principal Investigator

DEGUCHI Kimiko  慶應義塾大学, 医学部(信濃町), 講師(非常勤) (50227542)

Co-Investigator(Kenkyū-buntansha) 久保 健一郎  慶應義塾大学, 医学部(信濃町), 准教授 (20348791)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords超早産児 / 虚血性脳障害 / 神経学的後遺症 / 認知機能障害 / 自閉スペクトラム症 / 注意欠如多動症 / 発達神経症 / 細胞移動 / モデルマウス / トランスクリプトーム解析 / 環境要因 / 行動試験 / 認知機能 / 子宮内胎児電気穿孔法 / フラッシュ・タグ法 / 虚血 / 脳障害 / エレクトロポレーション / 神経細胞移動 / シナプス / 超早産 / 後遺症 / 発達障害 / マウスモデル
Outline of Final Research Achievements

In this study, we used our unique mouse model of ischemic brain damage, in which cognitive impairments occur after birth by temporarily occluding the uterine arteries in pregnant mice. This mouse model is considered as a good model for the neurological impairments of ischemic brain damage in extremely preterm infants. We analyzed whether impaired neuronal migrations caused by ischemic brain damage during development result in morphological changes in spines after birth. Furthermore, we analyzed the changes in gene expression profiles of neurons that show impaired migrations. As a result of transcriptome analysis using next generation sequencing and microarray analysis, changes in gene expression profiles were detected in molecular pathways related to cognitive functions. These changes might underlie cognitive impairments in extremely preterm infants and would be important as candidates for future therapeutic targets.

Academic Significance and Societal Importance of the Research Achievements

超早産児の虚血性脳障害による神経学的後遺症の特徴としては、これまでのような脳性麻痺などの運動発達障害が主体ではなく、認知機能障害や、自閉スペクトラム症や注意欠如多動症のような発達神経症(発達障害)の頻度が高い事が注目されている。本研究によって、発達段階における虚血性脳障害という環境要因によって、認知機能に関わる分子経路の遺伝子発現が変化して、これが生後の認知機能障害に関わる可能性が示された。これらの分子経路は、治療標的の候補となるため、今後、超早産児の虚血性脳障害による神経学的後遺症に対する治療開発を進めていく上で、基盤となる重要な所見が得られた。

Report

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

    (17 results)

All 2020 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (13 results) (of which Int'l Joint Research: 4 results,  Invited: 9 results)

  • [Journal Article] Human neocortical development as a basis to understand mechanisms underlying neurodevelopmental disabilities in extremely preterm infants2020

    • Author(s)
      Kubo Ken‐ichiro、Deguchi Kimiko
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: 46 Issue: 11 Pages: 2242-2250

    • DOI

      10.1111/jog.14468

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased densities of white matter neurons as a cross‐disease feature of neuropsychiatric disorders2020

    • Author(s)
      Kubo Ken‐ichiro
    • Journal Title

      Psychiatry and Clinical Neurosciences

      Volume: 74 Issue: 3 Pages: 166-175

    • DOI

      10.1111/pcn.12962

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Both excitatory and inhibitory neurons transiently form clusters at the outermost region of the developing mammalian cerebral neocortex2019

    • Author(s)
      Shin Minkyung、Kitazawa Ayako、Yoshinaga Satoshi、Hayashi Kanehiro、Hirata Yukio、Dehay Colette、Kubo Ken‐ichiro、Nakajima Kazunori
    • Journal Title

      Journal of Comparative Neurology

      Volume: 527 Issue: 10 Pages: 1577-1597

    • DOI

      10.1002/cne.24634

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Drebrin-like (Dbnl) Controls Neuronal Migration via Regulating N-Cadherin Expression in the Developing Cerebral Cortex2018

    • Author(s)
      Inoue Seika、Hayashi Kanehiro、Fujita Kyota、Tagawa Kazuhiko、Okazawa Hitoshi、Kubo Ken-ichiro、Nakajima Kazunori
    • Journal Title

      The Journal of Neuroscience

      Volume: 39 Issue: 4 Pages: 678-691

    • DOI

      10.1523/jneurosci.1634-18.2018

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 発生段階における虚血等による脳傷害が脳の発達に与える影響の解析2020

    • Author(s)
      久保健一郎、出口貴美子、吉永怜史、野々村美康、大島鴻太、高杉聡、北澤彩子、井上健、仲嶋一範
    • Organizer
      第123回日本小児科学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Extremely preterm infants with brain injury leads to cognitive dysfunction due to neuronal brain network damage2019

    • Author(s)
      Kimiko Deguchi, Ken-ichiro Kubo, Kazunori Nakajima, Ken Inoue
    • Organizer
      15th Asian and Oceanian Congress of Child Neurology (AOCCN) & 41st Malaysian Paediatric Association Annual Congress 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 神経細胞移動の障害が超早産児の認知機能低下に関与する可能性についての検討2019

    • Author(s)
      久保 健一郎,出口 貴美子,井上 健,仲嶋 一範
    • Organizer
      第24回認知神経科学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 脳の細胞構築に注目して精神疾患の病態を理解する試みについて2019

    • Author(s)
      久保 健一郎,出口 貴美子,井上 健,仲嶋 一範
    • Organizer
      第115回 日本精神神経学会学術総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] New aspects of extremely preterm infants with brain injury2019

    • Author(s)
      Kimiko Deguchi, Ken-ichiro Kubo, Kazunori Nakajima, Ken Inoue
    • Organizer
      The 20th Annual Meeting of Infantile Seizure Society
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 超早産児脳の最近の知見 ─NICUのその後をどう育むか?─ 在胎20-28週のヒト脳の脆弱性2019

    • Author(s)
      出口 貴美子、久保 健一郎、井上 健、仲嶋 一範
    • Organizer
      第4回小児ニューロリハビリテーション研究会・第4回超早産児神経発達症研究会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 超早産児虚血モデルマウスの開発と応用2019

    • Author(s)
      久保 健一郎,出口 貴美子,井上 健,仲嶋 一範
    • Organizer
      第4回小児ニューロリハビリテーション研究会・第4回超早産児神経発達症研究会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 超早産児虚血性脳障害モデルマウスの解析と治療戦略2018

    • Author(s)
      久保健一郎、出口貴美子、ハズラ デバブラタ、吉永怜史、井上健、仲嶋一範
    • Organizer
      日本新生児生育医学会・学術集会サテライトセミナー
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 神経発達症モデルマウスの作成とその神経回路の解析2018

    • Author(s)
      久保健一郎、出口貴美子、石井一裕、井上健、仲嶋一範
    • Organizer
      2018年度生理学研究所研究会 「情動の神経回路機構とその破綻」
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Pathogenesis of neurodevelopmental disorders in extremely preterm infants2018

    • Author(s)
      Kimiko Deguchi, Ken-ichiro Kubo, Ken Inoue, and Kazunori Nakajima
    • Organizer
      11th FENS Forum of Neuroscience
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pathophysiology of neuronal network damage in the mouse model of extremely preterm infants2018

    • Author(s)
      Kimiko Deguchi, Ken-ichiro Kubo, Ken Inoue, and Kazunori Nakajima
    • Organizer
      第60回日本小児神経学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Neuronal network damage in mouse model of extremely preterm infants with brain injury2018

    • Author(s)
      Kimiko Deguchi, Ken-ichiro Kubo, Ken Inoue, and Kazunori Nakajima
    • Organizer
      22nd Biennial Meeting of the International Society for Developmental Neuroscience (ISDN2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 超早産児における神経発達症の新たな知見と治療戦略2018

    • Author(s)
      出口貴美子、久保健一郎、井上健、仲嶋一範
    • Organizer
      第121回日本小児科学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited

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

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