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Elucidation of a preventive strategy against diabetic dementia induced by blood-brain barrier disruption

Research Project

Project/Area Number 25462220
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionEhime University

Principal Investigator

MOGI MASAKI  愛媛大学, 医学(系)研究科(研究院), 准教授 (20363236)

Co-Investigator(Kenkyū-buntansha) HORIUCHI Masatsugu  愛媛大学, 大学院医学系研究科, 教授 (40150338)
IWANAMI Jun  愛媛大学, 大学院医学系研究科, 助教 (90624792)
Co-Investigator(Renkei-kenkyūsha) OHSHIMA Kousei  愛媛大学, 大学院医学系研究科, 医員 (10598626)
TSUKUDA Kana  愛媛大学, 大学院医学系研究科, 研究員 (90647653)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords糖尿病 / 認知機能 / 血液脳関門 / レニン・アンジオテンシン系 / AT2受容体
Outline of Final Research Achievements

Type 2 diabetes mellitus has been highlighted as a major risk factor for cognitive decline associated with not only vascular dementia but also Alzheimer disease.We previously reported that BBB disruption was involved in T2DM-induced cognitive impairment.Here,we further investigated the relation between BBB disruption and diabetes. Results are shown below.
(1) In diabetic mice, KKAy, BBB disruption is occurred at first. Then, vascular dysfunction may be spread out to small vessel disease via time-course observation of KKAy brain (unpublished data). (2) Renin-angiotensin system may be involving BBB disruption via evaluation of BBB in human-renin and human-angiotensinogen overexpressed mice. (3) Angiotensin II type 2 receptor stimulation has a preventive effect on diabetic dementia and vascular dementia models using direct AT2 receptor stimulation with C21. Therefore, AT2 receptor stimulation may have a potential as new therapeutical approach for diabetic dementia.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (10 results)

All 2015 2014 Other

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Invited: 4 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Direct angiotensin II type 2 receptor stimulation by compound 21 prevents vascular dementia.2015

    • Author(s)
      Iwanami J, Mogi M, Tsukuda K, Wang XL, Nakaoka H, Kan-no H, Chisaka T, Bai HY, Shan BS, Kukida M, Horiuchi M.
    • Journal Title

      J Am Soc Hypertens

      Volume: 9 Issue: 4 Pages: 250-256

    • DOI

      10.1016/j.jash.2015.01.010

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Possible synergistic effect of direct angiotensin II type 2 receptor stimulation by compound 21 with memantine on prevention of cognitive decline in type 2 diabetic mice.2014

    • Author(s)
      Iwanami J, Mogi M, Tsukuda K, Jing F, Ohshima K, Wang XL, Nakaoka H, Kan-no H, Chisaka T, Bai HY, Min LJ, Horiuchi M.
    • Journal Title

      Eur J Pharmacol

      Volume: 724 Pages: 9-15

    • DOI

      10.1016/j.ejphar.2013.12.015

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Neuroinflammation and Hypertension2015

    • Author(s)
      茂木正樹
    • Organizer
      第38回日本高血圧学会総会
    • Place of Presentation
      愛媛県松山市
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 認知症と高血圧2015

    • Author(s)
      茂木正樹
    • Organizer
      第34回日本認知症学会学術集会
    • Place of Presentation
      青森県青森市
    • Year and Date
      2015-10-02
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 脳のアンチエイジング-Next Decade-2015

    • Author(s)
      茂木正樹
    • Organizer
      第15回日本抗加齢医学会総会
    • Place of Presentation
      福岡県福岡市
    • Year and Date
      2015-05-29
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] アンジオテンシンII 2型受容体 活性化による臓器保護作用

    • Author(s)
      茂木正樹
    • Organizer
      第36回 日本高血圧学会
    • Place of Presentation
      大阪国際会議場
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Possible Synergistic Effect of Direct Angiotensin II Type 2 Receptor Stimulation by Compound 21 with Memantine on Cognitive Impairment in Type 2 Diabetic Mouse

    • Author(s)
      Masaki Mogi, Jun Iwanami, Hirotomo Nakaoka, Kana Tsukuda, Kousei Ohshima, Jing Fei, Xiaoli Wang, Toshiyuki Chisaka, Li-Juan Min and Masatsugu Horiuchi
    • Organizer
      The Alzheimer's Association International Conference
    • Place of Presentation
      Boston, MA, USA
    • Related Report
      2013 Research-status Report
  • [Book] The Protective Arm of the Renin Angiotensin System (RAS), Functional Aspects and Therapeutic Implications2015

    • Author(s)
      Mogi M, Horiuchi M
    • Total Pages
      6
    • Publisher
      Academic Press, Boston
    • Related Report
      2015 Annual Research Report
  • [Remarks] 愛媛大学大学院医学系研究科 分子心血管生物・薬理学ホームページ

    • URL

      http://www.m.ehime-u.ac.jp/school/biochem1/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 愛媛大学大学院医学系研究科 分子心血管生物・薬理学

    • URL

      http://www.m.ehime-u.ac.jp/school/biochem1/

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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