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Childhood nutrition-dependent myelin structure and its effects on psychiatric symptoms

Research Project

Project/Area Number 20H03604
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 52030:Psychiatry-related
Research InstitutionNara Medical University

Principal Investigator

Makinodan Manabu  奈良県立医科大学, 医学部, 准教授 (00510182)

Co-Investigator(Kenkyū-buntansha) 栗本 一基  奈良県立医科大学, 医学部, 教授 (20415152)
鳥塚 通弘  奈良県立医科大学, 医学部, 講師 (20588529)
山室 和彦  奈良県立医科大学, 医学部, 学内講師 (60526721)
末次 志郎  奈良先端科学技術大学院大学, 先端科学技術研究科, 教授 (70345031)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2022: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2020: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Keywords栄養 / エライジン酸 / オレイン酸 / 炎症 / 髄鞘 / 前頭前野 / 社会行動 / 社会性 / ミクログリア / 髄鞘形成 / 脂肪酸 / 小児期 / 脂質 / マウス / 小児期体験 / 運動
Outline of Research at the Start

ネグレクトなどの虐待は様々な精神疾患を引き起こす。応募者らは、ネグレクトを模した幼若期隔離マウスの前頭前野髄鞘形成および同部位の機能低下を明らかにした。一方、約80%が脂質で構成される髄鞘では、幼若期に取り込まれた脂肪酸組成が成体期まで長期にわたり保持される。本研究課題では、幼若期の脂質栄養環境が前頭前野の髄鞘構造、前頭前野機能および行動にどのような変化を与えるのかなどを最先端の技術を用いて多面的に解析し、前頭前野の髄鞘形成に関与する脂質動態基盤を明らかにする。次に、これらの結果を踏まえ、幼若期隔離マウスの前頭前野髄鞘形成障害を改善する方法(脂質栄養介入、運動介入)を探索する。

Outline of Final Research Achievements

Adverse childhood experiences such as neglect have long-term negative psychological effects, and the present study examined the effects of childhood trans-fatty acid intake status on later social behavior. It was hypothesized that elaidinic acid would be incorporated into the myelin sheath only after administration from P11 to P45, when the development of myelination is most pronounced, and that it would alter the structure of the myelin sheath over a long period of time. Since social behavior was impaired only in the juvenile elaidinic acid group, RNA-seq and single-microglial RNA-seq evaluation revealed a markedly increased inflammatory response and abnormalities in specific microglial clusters in the juvenile elaidinic acid group.

Academic Significance and Societal Importance of the Research Achievements

コロナ禍により児童虐待件数はさらに増加して大きな社会問題となっているが、ネグレクトなどによる不良な栄養環境がのちのメンタルヘルスや脳機能にどういった影響を与えるのかは不明である。本研究では、幼若期と成体期のマウスにマーガリンなどに含まれるトランス脂肪酸(エライジン酸)と投与し、児童虐待児で認められる髄鞘形成障害や脳内炎症について調べたところ、幼若期に投与されたマウスは社会性が低下し、特定のマイクログリア群が異常となることが確認された。これらの結果により、幼若期の脂質栄養環境は成体期よりも社会性などに悪影響を及ぼすことが示唆された。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (10 results)

All 2023 2022 2021 2020

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

  • [Journal Article] Juvenile social isolation affects the structure of the tanycyte-vascular interface in the hypophyseal portal system of the adult mice.2023

    • Author(s)
      1.Takemura S, Ayami Isonishi, Horii-Hayashi N, Tanaka T, Tatsumi K, Komori T, Yamamuro K, Yamano M, Nishi M, Makinodan M, Wanaka A.
    • Journal Title

      Neurochem. Int

      Volume: 162 Pages: 105439-105439

    • DOI

      10.1016/j.neuint.2022.105439

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Juvenile social isolation immediately affects the synaptic activity and firing property of fast-spiking parvalbumin-expressing interneuron subtype in mouse medial prefrontal cortex2022

    • Author(s)
      Okamura Kazuya、Yoshino Hiroki、Ogawa Yoichi、Yamamuro Kazuhiko、Kimoto Sohei、Yamaguchi Yasunari、Nishihata Yosuke、Ikehara Minobu、Makinodan Manabu、Saito Yasuhiko、Kishimoto Toshifumi
    • Journal Title

      Cerebral Cortex

      Volume: 33 Issue: 7 Pages: 3591-3606

    • DOI

      10.1093/cercor/bhac294

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The effects of maternal separation on behaviours under social-housing environments in adult male C57BL/6 mice2021

    • Author(s)
      Endo Nozomi、Makinodan Manabu、Mannari-Sasagawa Takayo、Horii-Hayashi Noriko、Somayama Nami、Komori Takashi、Kishimoto Toshifumi、Nishi Mayumi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 527-527

    • DOI

      10.1038/s41598-020-80206-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maternal immune activation affects hippocampal excitatory and inhibitory synaptic transmission in offspring from an early developmental period to adulthood.2020

    • Author(s)
      6.Nakagawa K, Yoshino H, Ogawa Y, Yamamuro K, Kimoto S, Noriyama Y, Makinodan M, Yamashita M, Saito Y, Kishimoto T
    • Journal Title

      Font Cell Neurosci

      Volume: 14 Pages: 241-241

    • DOI

      10.3389/fncel.2020.00241

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Juvenile Social Isolation Enhances the Activity of Inhibitory Neuronal Circuits in the Medial Prefrontal Cortex.2020

    • Author(s)
      Yamamuro K, Yoshino H, Ogawa Y, Okamura K, Nishihata Y, Makinodan M, Saito Y, Kishimoto T
    • Journal Title

      Front Cell Neurosci

      Volume: 14 Pages: 105-105

    • DOI

      10.3389/fncel.2020.00105

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ミクログリアBDNFと前頭前野のE-Iバランス2022

    • Author(s)
      牧之段学
    • Organizer
      BPCNPNPPP4大会合同大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 自閉スペクトラム症におけるE-Iバランス2022

    • Author(s)
      牧之段学
    • Organizer
      日本精神神経学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 自閉スペクトラム症の心理的不適応が引き起こす諸問題の生物学的検討2021

    • Author(s)
      牧之段学
    • Organizer
      日本認知・行動療法学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 臨床精神科医だからできる神経化学研究2021

    • Author(s)
      牧之段学
    • Organizer
      日本精神神経学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Juvenile brain-derived neurotrophic factor from microglia regulates social behavior in adult mice.2020

    • Author(s)
      1.Makinodan M, Komori T, Okamura K, Yamamuro K, Ikehara M, Endo N, Nishi M, Kishimoto T
    • Organizer
      American College of Neuropsychopharmacology
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research

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Published: 2020-04-28   Modified: 2024-01-30  

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