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Unraveling mechanism for the remote effects of vascular inflammation on cognitive dysfunction using a mice model of abdominal aortic aneurysm

Research Project

Project/Area Number 16K09233
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General internal medicine(including psychosomatic medicine)
Research InstitutionThe University of Tokyo

Principal Investigator

SON Bo-Kyung  東京大学, 高齢社会総合研究機構, 特任助教 (20625256)

Co-Investigator(Kenkyū-buntansha) 伊藤 公一  東京大学, 大学院農学生命科学研究科(農学部), 特任准教授 (50330874)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords血管炎症 / 認知機能低下 / 慢性炎症 / 臓器老化の階層構造 / 血管老化 / マクロファージ / 神経炎症 / 認知機能 / 性ホルモン / 炎症性サイトカイン / 神経障害 / 臓器連関
Outline of Final Research Achievements

In the present study, to unravel the hierarchical pathway from vascular pathologies to cognitive dysfunction, we examined effects of abdominal aortic aneurysm induced by inflammation on cognitive function, using a reliable mouse model. Significant decline of cognitive function was seen in vascular aneurysm induced mice, compared to 12 months-old male sham mice. Furthermore, decrease in number of neuronal cells and increase in number of activated microglia were observed, implying the remote effects of vascular aneurysm on neuronal inflammation and aging. Mechanistically, augment of circulating interleukins contributes this inflammatory expansion from vessel to hippocampus.

Academic Significance and Societal Importance of the Research Achievements

本研究では血管病変を上流ととらえた認知機能低下への階層関係について、慢性炎症を中心に明らかにした。今後、更なる研究により、中核因子の同定やその因子の制御による病変の抑制および機能改善が明らかにすることで、老年疾患の連鎖を断ち切る新たな治療策を提案でき、健康寿命延長に寄与すると期待できる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (27 results)

All 2019 2018 2017 2016

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (24 results) (of which Int'l Joint Research: 8 results)

  • [Journal Article] Establishment of Novel Murine Model showing Vascular Inflammation-derived Cognitive Dysfunction.2019

    • Author(s)
      Hashizume T, Son BK, Taniguchi S, Ito K, Noda Y, Endo T, Nanao-Hamai M, Ogawa S, Akishita M.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 4023-4034

    • DOI

      10.1038/s41598-019-40726-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low-intensity exercise suppresses C/EBPdelta/myostatin pathway through androgen receptor in muscle cells2019

    • Author(s)
      Son BK, Eto M, Oura M, Ishida Y, Taniguchi S, Ito K, Umeda-Kameyama Y, Kojima T, Akishita M
    • Journal Title

      Gerontology

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sex difference in the association of androgens with aortic calcification.2018

    • Author(s)
      Hashizume T, Son BK, Kojima T, Nanao-Hamai M, Asari Y, Umeda-Kameyama Y, Ogawa S, Akishita M.
    • Journal Title

      Geriatr Gerontol Int.

      Volume: 18 Issue: 7 Pages: 1137-1138

    • DOI

      10.1111/ggi.13306

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Low-intensity exercise suppresses myostatin pathway through androgen receptor in muscle cells2019

    • Author(s)
      Son BK, Eto M, Ishida Y, Oura M, Akishita M
    • Organizer
      International Conference on Sarcopenia & Frailty Research
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] テストステロンは炎症抑制作用を介して大動脈瘤の形成を抑制する2019

    • Author(s)
      孫輔卿, 小川純人, 秋下雅弘
    • Organizer
      第12回日本性差医学・医療学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 雄マウスでの低強度運動は筋内のテストステロン分泌を亢進し、筋分解を抑制する2019

    • Author(s)
      孫輔卿, 江頭正人, 大浦美弥, 秋下雅弘
    • Organizer
      第12回日本性差医学・医療学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Testosterone inhibits aortic aneurysm formation through suppression of inflammation2018

    • Author(s)
      Son BK, Ogawa S, Akishita M
    • Organizer
      the Gerontological Society of America
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sex difference in the association of androgens with aortic calcification2018

    • Author(s)
      Hashizume T, Son BK, Kojima T, Nanao-Hamai M, Asari Y, Umeda-Kameyama Y, Ogawa S, Akishita M
    • Organizer
      XIX ISA world congress of society
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 加齢に伴う血管炎症の認知機能への影響 ―大動脈瘤マウスモデルを用いた検討―2018

    • Author(s)
      橋詰剛、孫輔卿、濵井道子、小川純人、秋下雅弘
    • Organizer
      第50回日本動脈硬化学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] テストステロンの炎症抑制作用を介した大動脈瘤形成の抑制効果2018

    • Author(s)
      孫輔卿、小川純人、秋下雅弘
    • Organizer
      第50回日本動脈硬化学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 大動脈瘤形成に対するテストステロンの抑制作用と炎症の制御 -精巣摘出マウスを用いた検討-2017

    • Author(s)
      孫 輔卿、小川 純人、秋下 雅弘
    • Organizer
      第8回テストステロン研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] Preventive effects of testosterone/androgen receptor against the formation of abdominal aortic aneurysm in mice2017

    • Author(s)
      Son BK, Ogawa S, Akishita M
    • Organizer
      8th Congress of the International Society for Gender Medicine
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Estrogen inhibits vascular smooth muscle cells calcification through estrogen receptor alpha-dependent Gas6 transactivation2017

    • Author(s)
      Son BK, Ogawa S, Akishita M
    • Organizer
      8th Congress of the International Society for Gender Medicine
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Preventive effects of testosterone on development of abdominal aortic aneurysm2017

    • Author(s)
      Son BK, Ogawa S, Akishita M
    • Organizer
      21st International Association of Gerontology and Geriatrics (IAGG) World Congress
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 低テストステロンによる大動脈瘤形成と炎症の関与 -精巣摘出マウスを用いた検討2017

    • Author(s)
      孫 輔卿、小川 純人、秋下 雅弘
    • Organizer
      第49回日本動脈硬化学会
    • Related Report
      2017 Research-status Report
  • [Presentation] テストステロン低下による大動脈瘤形成の促進と炎症の関与 -精巣摘出マウスを用いた検討-2017

    • Author(s)
      孫 輔卿、小川 純人、秋下 雅弘
    • Organizer
      第59回日本老年学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Ginsenoside Rb1の血管石灰化抑制作用  -選択的アンドロゲン受容体モジュレーター(SARM)としての可能性-2017

    • Author(s)
      濵井道子、孫 輔卿、小川 純人、秋下 雅弘
    • Organizer
      第59回日本老年学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Ginsenoside Rb1 Inhibited Vascular Smooth Muscle Cells Calcification through Androgen Receptor2017

    • Author(s)
      Nanao-Hamai M, Son BK, Hashizume T, Ogawa S, Akishita M
    • Organizer
      21st International Association of Gerontology and Geriatrics (IAGG) World Congress
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 大動脈瘤による認知機能低下への影響 ―炎症制御破綻を介した作用―2017

    • Author(s)
      橋詰剛、孫輔卿、濵井道子、小川純人、秋下雅弘
    • Organizer
      第8回日本脳血管・認知症学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 大動脈瘤の認知機能低下への影響 ―大動脈瘤マウスモデルを用いた検討―2017

    • Author(s)
      橋詰剛、孫輔卿、濵井道子、小川純人、秋下雅弘
    • Organizer
      第49回日本動脈硬化学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Characteristics of age-related skeletal muscle decline and cognitive impairment in mouse: Influence of vascular inflammation2017

    • Author(s)
      Hashizume T, Son BK, Nanao-Hamai M, Ogawa S, Akishita M
    • Organizer
      International conference on frail & sarcopenia research (ICFSR)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Testosterone deficiency proceeds abdominal aortic aneurysm through exuberant inflammation2016

    • Author(s)
      孫 輔卿
    • Organizer
      日本動脈硬化学会
    • Place of Presentation
      東京、京王プラザホテル
    • Year and Date
      2016-07-14
    • Related Report
      2016 Research-status Report
  • [Presentation] 腹部大動脈瘤の形成・進行促進に対するinflammagingの関与 ― 老化促進モデルマウスを用いた検討 ―2016

    • Author(s)
      橋詰 剛
    • Organizer
      日本動脈硬化学会
    • Place of Presentation
      東京、京王プラザホテル
    • Year and Date
      2016-07-14
    • Related Report
      2016 Research-status Report
  • [Presentation] Effects of testosterone deficiency on development of abdominal aortic aneurysm2016

    • Author(s)
      孫 輔卿
    • Organizer
      Asian-Pacific Society of Atherosclerosis and Vascular Disease
    • Place of Presentation
      東京、京王プラザホテル
    • Year and Date
      2016-07-14
    • Related Report
      2016 Research-status Report
  • [Presentation] Role of inflammaging in abdominal aortic aneurysm: a study using senescence- accelerated prone mice2016

    • Author(s)
      橋詰 剛
    • Organizer
      Asian-Pacific Society of Atherosclerosis and Vascular Disease
    • Place of Presentation
      東京、京王プラザホテル
    • Year and Date
      2016-07-14
    • Related Report
      2016 Research-status Report
  • [Presentation] Testosterone deficiency promotes development of abdominal aortic aneurysm in mice.2016

    • Author(s)
      孫 輔卿
    • Organizer
      International and Interdisciplinary Symposium
    • Place of Presentation
      東京、東京医科歯科大学 鈴木記念講堂
    • Year and Date
      2016-07-11
    • Related Report
      2016 Research-status Report
  • [Presentation] Inflammaging accelerates abdominal aortic aneurysm formation and progression.2016

    • Author(s)
      橋詰 剛
    • Organizer
      International and Interdisciplinary Symposium
    • Place of Presentation
      東京、東京医科歯科大学 鈴木記念講堂
    • Year and Date
      2016-07-11
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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