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The relation between hypertension-related cognitive decline and neural insulin signaling

Research Project

Project/Area Number 19K21507
Project/Area Number (Other) 18H06432 (2018)
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund (2019)
Single-year Grants (2018)
Review Section 0909:Sports sciences, physical education, health sciences, and related fields
Research InstitutionNational Center for Geriatrics and Gerontology

Principal Investigator

Fukui Yusuke  国立研究開発法人国立長寿医療研究センター, 統合加齢神経科学研究部, 研究員 (60824802)

Project Period (FY) 2018-08-24 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords認知機能障害 / 糖尿病 / 高血圧 / 糖代謝 / 認知症 / 糖脂質代謝 / インスリンシグナル / 記憶学習能 / 老化 / インスリン受容体基質 / 代謝
Outline of Research at the Start

本研究では、高血圧を伴う糖尿病モデルマウスを用いて、代謝、脳・末梢組織のインスリンシグナルと認知機能の変化について解析する。また、神経変性改善作用を持つ脳IRS2シグナルの欠損が、高血圧および糖尿病により誘導される代謝標的組織のインスリンシグナルおよび認知機能の変化に与える影響について精査し、脳IRS2シグナル、糖脂質代謝、末梢組織のインスリンシグナル、認知機能の関連性について明らかにする。

Outline of Final Research Achievements

Middle-aged type2 diabetes (T2DM) model mice showed increased blood lipid level, cognitive impairment, and changes of glucose metabolism-related signaling factors without Aβ alteration. On the other hand, STZ-induced -type1 diabetes (T1DM) mice also showed cognitive impairment, however, no change of glucose metabolism-related signaling factors and Aβ level was observed. Moreover, middle-aged APPKI mice with increased Aβ level showed change of glucose metabolism-related signaling together with cognitive decline.

Academic Significance and Societal Importance of the Research Achievements

本研究は、栄養代謝異常を持つ認知機能障害モデルマウスを用いて、脳の糖代謝調節経路および代謝の変化と認知機能の関係について解析したもので学術的・社会的意義が深い。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • Research Products

    (14 results)

All 2020 2019 2018 2017

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 2 results) Presentation (6 results)

  • [Journal Article] Bone Marrow Stromal Cell Transplantation Drives Molecular Switch from Autophagy to the Ubiquitin-Proteasome System in Ischemic Stroke Mice2020

    • Author(s)
      Tadokoro Koh、Fukui Yusuke、Yamashita Toru、Liu Xia、Tsunoda Keiichiro、Shang Jingwei、Morihara Ryuta、Nakano Yumiko、Tian Feng、Sasaki Ryo、Matsumoto Namiko、Nomura Emi、Shi Xiaowen、Omote Yoshio、Takemoto Mami、Hishikawa Nozomi、Ohta Yasuyuki、Abe Koji
    • Journal Title

      Journal of Stroke and Cerebrovascular Diseases

      Volume: 29 Issue: 5 Pages: 104743-104743

    • DOI

      10.1016/j.jstrokecerebrovasdis.2020.104743

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Yoga-plus exercise mix promotes cognitive, affective, and physical functions in elderly people2019

    • Author(s)
      Hishikawa Nozomi、Takahashi Yoriko、Fukui Yusuke、Tokuchi Ryo、Furusawa Junichi、Takemoto Mami、Sato Kota、Yamashita Toru、Ohta Yasuyuki、Abe Koji
    • Journal Title

      Neurological Research

      Volume: 41 Issue: 11 Pages: 1001-1007

    • DOI

      10.1080/01616412.2019.1672380

    • NAID

      120006889321

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serine Phosphorylation of IRS1 Correlates with Aβ-Unrelated Memory Deficits and Elevation in Aβ Level Prior to the Onset of Memory Decline in AD2019

    • Author(s)
      Wang W, Tanokashira D, Fukui Y, Maruyama M, Kuroiwa C, Saito T, SaidoTC and Taguchi A
    • Journal Title

      Nutrients

      Volume: 11(8) Issue: 8 Pages: 1942-1942

    • DOI

      10.3390/nu11081942

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Unique Case with Oral Dyskinesia, Chorea, Ataxia, and Mild Cognitive Impairment with Caudate Atrophy and Characteristic Brain Calcifications2018

    • Author(s)
      Hishikawa N, Fukui Y, Sato K, Takemoto M, Yamashita T, Ohta Y, Abe K.
    • Journal Title

      Internal Medicine

      Volume: 57 Issue: 16 Pages: 2399-2402

    • DOI

      10.2169/internalmedicine.9454-17

    • NAID

      130007433443

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2018-08-15
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical predictors of Alzheimer's disease progression2018

    • Author(s)
      Hishikawa N, Fukui Y, Takemoto M, Sato K, Shang J, Yamashita T, Ohta Y, Abe K.
    • Journal Title

      Geriatr Gerontol Int.

      Volume: 18(6) Issue: 6 Pages: 929-936

    • DOI

      10.1111/ggi.13286

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic Effects of Pretreatment with Tocovid on Oxidative Stress in Postischemic Mice Brain.2018

    • Author(s)
      Shang J, Yan H, Jiao Y, Ohta Y, Liu X, Li X, Morihara R, Nakano Y, Fukui Y, Shi X, Huang Y, Feng T, Takemoto M, Sato K, Hishikawa N, Yamashita T, Abe K.
    • Journal Title

      J Stroke Cerebrovasc Dis.

      Volume: 27(8) Issue: 8 Pages: 2096-2105

    • DOI

      10.1016/j.jstrokecerebrovasdis.2018.03.012

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic cerebral hypoperfusion accelerates Alzheimer's disease pathology with the change of mitochondrial fission and fusion proteins expression in a novel mouse model.2018

    • Author(s)
      Feng T, Yamashita T, Zhai Y, Shang J, Nakano Y, Morihara R, Fukui Y, Hishikawa N, Ohta Y, Abe K.
    • Journal Title

      Brain Res.

      Volume: 1696 Pages: 63-70

    • DOI

      10.1016/j.brainres.2018.06.003

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detecting spinal pyramidal tract of amyotrophic lateral sclerosis patients with diffusion tensor tractography.2017

    • Author(s)
      Fukui Y, Hishikawa N, Sato K, Nakano Y, Morihara R, Shang J, Takemoto M, Ohta Y, Yamashita T, Abe K.
    • Journal Title

      Neurosci Res.

      Volume: Epub ahead of print Pages: 58-63

    • DOI

      10.1016/j.neures.2017.11.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Tractographyを用いた筋萎縮性側索硬化症における頚髄側索錐体路の損傷評価2020

    • Author(s)
      福井裕介、菱川望、表芳夫、武本麻美、太田康之、山下徹、阿部康二
    • Organizer
      第43回日本脳神経CI学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 2型糖尿病による海馬IRSシグナル変化とアルツハイマー病態との連関2019

    • Author(s)
      田之頭大輔、王 蔚、福井裕介、丸山めぐみ、黒岩智恵美、斉藤貴志、西道隆臣、田口明子
    • Organizer
      第28回海馬と高次脳機能学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] セリンリン酸化を介した海馬IRS1シグナルと認知機能障害の関係についての検討2019

    • Author(s)
      王 蔚、田之頭大輔、福井裕介、丸山めぐみ、黒岩智恵美、斉藤貴志、西道隆臣、田口明子
    • Organizer
      第28回海馬と高次脳機能学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 2型糖尿病が海馬IRSシグナルおよびアルツハイマー病態へ与える影響2019

    • Author(s)
      田之頭大輔、王 蔚、福井裕介、丸山めぐみ、黒岩智恵美、斉藤貴志、西道隆臣、田口明子
    • Organizer
      第34回日本糖尿病合併症学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 認知機能障害発症における海馬IRS1セリンリン酸化の役割2019

    • Author(s)
      王 蔚、田之頭大輔、福井裕介、丸山めぐみ、黒岩智恵美、斉藤貴志、西道隆臣、田口明子
    • Organizer
      第34回日本糖尿病合併症学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] メトホルミンは海馬IRS1活性化を介して糖尿病に伴う認知機能障害を改善する.2018

    • Author(s)
      田之頭大輔、福井裕介、佐藤駿介、柏田舞波、竹井喜美、丸山めぐみ、田口明子.
    • Organizer
      第33回日本糖尿病合併症学会
    • Related Report
      2018 Annual Research Report

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Published: 2018-08-27   Modified: 2024-03-26  

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