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Elucidation of pathogenic mechanism of sociality impaired dementia

Research Project

Project/Area Number 18K07354
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 51020:Cognitive and brain science-related
Research InstitutionSaitama Medical University

Principal Investigator

Maruyama Kei  埼玉医科大学, 医学部, 教授 (30211577)

Co-Investigator(Kenkyū-buntansha) 吉川 圭介  埼玉医科大学, 医学部, 講師 (10435860)
柳下 楠  埼玉医科大学, 医学部, 助教 (70799189)
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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsニューロリギン / ニューレキシン / 認知症 / テストステロン / シナプス接着分子 / デグー / アルツハイマー病 / タウ / neuroligin / tau / 前頭側頭葉変性症
Outline of Final Research Achievements

Sociality is one of the main functions of human activities and impaired in dementia. We focused on Neurexin and Neuroligin as sociality-related genes, which are genetically related to autism spectrum disorder in human. Recently, they are also said to be related to Alzheimer disease. Neurexin and Neuroligin are localized at pre- and post-synapses, respectively. They bind each other to exert effects of synaptic differentiation and maturation. Therefore, we explored effectors on the Neurexin-Neuroligin binding. According to our results, testosterone, one of the male hormones, directly binds to Neurexin and intercepts intercellular Neurexin-Neuroligin binding. Moreover, it is of high interest that testosterone is another key molecule of the higher incidence of autism in male. These results may promote understanding toward the pathogenic mechanism of sociality impaired dementia.

Academic Significance and Societal Importance of the Research Achievements

日常生活を営む上で、多大な影響が出てしまう認知症の中でも、記憶障害に関する知見や研究は日々進んでいる。しかしその一方で、認知症が呈する他の症状については、その影響に反して理解が深まっていないのが現状である。本研究により、認知症によって引き起こされる社会的行動の分子メカニズムの一端を明らかにした。その事自体が学術的に重要な意義を果たしているが、更には、認知症による社会的行動の障害がどのような分子のどのような働きによって起こっているかを明らかにすることで、症状の改善のためにどのような処置を行えば良いのか、探索するために重要な知見となる。

Report

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

    (12 results)

All 2021 2020 2019 2018

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

  • [Journal Article] Testosterone interrupts binding of Neurexin and Neuroligin that are expressed in a highly socialized rodent, Octodon degus2021

    • Author(s)
      Yagishita-Kyo Nan、Ikai Yuki、Uekita Tomoko、Shinohara Akio、Koshimoto Chihiro、Yoshikawa Keisuke、Maruyama Kei、Yagishita Sosuke
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 551 Pages: 54-62

    • DOI

      10.1016/j.bbrc.2021.03.015

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Galectin 3?binding protein suppresses amyloid-β production by modulating β-cleavage of amyloid precursor protein2020

    • Author(s)
      Seki Tsuneyoshi、Kanagawa Motoi、Kobayashi Kazuhiro、Kowa Hisatomo、Yahata Naoki、Maruyama Kei、Iwata Nobuhisa、Inoue Haruhisa、Toda Tatsushi
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 11 Pages: 3678-3691

    • DOI

      10.1074/jbc.ra119.008703

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sexually Dimorphic Regulation of Behavioral States by Dopamine in Caenorhabditis elegans2019

    • Author(s)
      Suo Satoshi、Harada Kazuki、Matsuda Shogo、Kyo Koki、Wang Min、Maruyama Kei、Awaji Takeo、Tsuboi Takashi
    • Journal Title

      The Journal of Neuroscience

      Volume: 39 Issue: 24 Pages: 4668-4683

    • DOI

      10.1523/jneurosci.2985-18.2019

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 記憶学習およびアミロイドβタンパク質に対する森林由来天然資源の効果2020

    • Author(s)
      阿部琴絵、岩佐健介、浅井将、丸山敬、清水邦義、吉川圭介
    • Organizer
      第29回神経行動薬理若手の集い
    • Related Report
      2019 Research-status Report
  • [Presentation] ウルソール酸の脱髄抑制効果2020

    • Author(s)
      酒本千誠、山本梓司、岩佐健介、丸山敬、清水邦義、吉川圭介
    • Organizer
      第29回神経行動薬理若手の集い
    • Related Report
      2019 Research-status Report
  • [Presentation] 脱髄モデルマウスにおける食用キノコの脱髄抑制効果2020

    • Author(s)
      武田乃ノ佳、山本梓司、岩佐健介、丸山敬、清水邦義、吉川圭介
    • Organizer
      第29回神経行動薬理若手の集い
    • Related Report
      2019 Research-status Report
  • [Presentation] 遺伝子改変によらないアルツハイマー病モデル・デグー2019

    • Author(s)
      柳下‐姜楠、蜜澤千春、小杉山捷、上北朋子、丸山敬、伊海結貴、篠原明男、越本知大、柳下聡介
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 高度な社会性を有する齧歯類O.degusの遺伝情報を用いた新たな自閉症スペクトラム障害発症メカニズムの解明2019

    • Author(s)
      柳下‐姜楠、上北朋子、伊海結貴、篠原明男、越本知大、柳下聡介、丸山敬
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Cyclic phosphatidic acid derivative is a novel drug candidate for multiple sclerosis2019

    • Author(s)
      Yamamoto S, Iwasa K, Gotoh M, Maruyama K, Murofushi K, Yoshikawa K
    • Organizer
      7th China-Japan joint meeting of basic and clinical pharmacology
    • Related Report
      2019 Research-status Report
  • [Presentation] Sexually dimorphic dopaminergic signaling regulates behavioral states of C. elegans2019

    • Author(s)
      Suo S, Harada K, Matsuda S, Kyo K, Wang M, Maruyama K, Awaji T, Tsuboi T
    • Organizer
      International C. elegans Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ドーパミンは線虫C. elegansの運動量の性差を生み出す2019

    • Author(s)
      周防 諭、原田 一貴、松田 翔吾、姜興起、王 旻、丸山 敬、淡路 健雄、坪井 貴司
    • Organizer
      Neuro2019 日本神経科学会大会・日本神経化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 社会性に関わるシナプス接着分子に対する性ホルモンの影響2018

    • Author(s)
      柳下‐姜楠、原田美海、上北朋子、丸山敬、伊海結貴、越本知大、柳下聡介
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Research-status Report

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

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