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Exacerbating effects of insulin resistance on Alzheimer's disease

Research Project

Project/Area Number 15K19279
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General internal medicine(including psychosomatic medicine)
Research InstitutionChiba University

Principal Investigator

Izuo Naotaka  千葉大学, 大学院医学研究院, 日本学術振興会特別研究員(PD) (50722261)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsアルツハイマー病 / 糖尿病 / インスリン抵抗性 / 行動解析 / 行動試験 / オメガ3脂肪酸 / メタボリックシンドローム / アミロイドベータ
Outline of Final Research Achievements

Insulin resistance is one of risk factors of Alzheimer’s disease (AD). I investigated an exacerbating effects of insulin resistance on AD by phenotypic analyses on model mice. By crossbreeding of insulin resistant mice knocked in mutant insulin receptor and AD model mice, we generated insulin resistant AD model mice. This double knockin mice exhibited deficit of long term memory, decreased anxiety sensitivity and depression in behavioral analyses without affecting senile plaque pathology. By oral administration of Omega-3 fatty acids, insulin resistant AD model mice recovered from psychological symptoms, especially depression. These results would contribute to developing preventive and therapeutic strategies on AD.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (29 results)

All 2018 2017 2016 2015 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 5 results,  Acknowledgement Compliant: 3 results) Presentation (21 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] アミロイドβ「毒性コンホマー」を標的にしたアルツハイマー病の治療・診断法の開発2018

    • Author(s)
      泉尾直孝、清水孝彦、村上一馬、入江一浩
    • Journal Title

      医薬品医療機器レギュラトリーサイエンス

      Volume: 印刷中

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Topical Application of Trisodium Ascorbyl 6-Palmitate 2-Phosphate Actively Supplies Ascorbate to Skin Cells in an Ascorbate Transporter-Independent Manner2017

    • Author(s)
      Shibuya Shuichi、Sakaguchi Ikuyo、Ito Shintaro、Kato Eiko、Watanabe Kenji、Izuo Naotaka、Shimizu Takahiko
    • Journal Title

      Nutrients

      Volume: 9 Issue: 7 Pages: 645-645

    • DOI

      10.3390/nu9070645

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A toxic conformer of Aβ42 with a turn at 22-23 is a novel therapeutic target for Alzheimer’s disease2017

    • Author(s)
      Naotaka Izuo, Chihiro Kasahara, Kazuma Murakami, Toshiaki Kume, Masahiro Maeda, Kazuhiro Irie, Koutaro Yokote, Takahiko Shimizu
    • Journal Title

      Sci. Rep.

      Volume: 7 Issue: 1 Pages: 11811-11811

    • DOI

      10.1038/s41598-017-11671-6

    • NAID

      120006368174

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Monoclonal antibody with conformational specificity for a toxic conformer of amyloid β42 and its application toward the Alzheimer's disease diagnosis2016

    • Author(s)
      Kazuma Murakami, Maki Tokuda, Takashi Suzuki, Yumi Irie, Mizuho Hanaki, Naotaka Izuo, Yoko Monobe, Ken-ichi Akagi, Ryotaro Ishii, Harutsugu Tatebe, Takahiko Tokuda, Masahiro Maeda, Toshiaki Kume, Takahiko Shimizu, Kazuhiro Irie
    • Journal Title

      Sci. Rep.

      Volume: 6 Issue: 1 Pages: 29038-29038

    • DOI

      10.1038/srep29038

    • NAID

      120005774689

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Resveratrol derivative-rich melinjo seed extract attenuates skin atrophy in Sod1-deficient mice.2015

    • Author(s)
      Watanabe, K., Shibuya, S., Ozawa, Y., Izuo, N., Shimizu, T.
    • Journal Title

      Oxid. Med. Cell. Longev.

      Volume: 2015 Pages: 391075-391075

    • DOI

      10.1155/2015/391075

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Brain-specific superoxide dismutase 2 deficiency causes perinatal death with spongiform encephalopathy in mice.2015

    • Author(s)
      Izuo, N., Nojiri, H., Uchiyama, S., Noda, Y., Kawakami, S., Kojima, S., Sasaki, T., Shirasawa, T., Shimizu, T.
    • Journal Title

      Oxid. Med. Cell. Longev.

      Volume: 2015 Pages: 238914-238914

    • DOI

      10.1155/2015/238914

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] アルツハイマー病様神経毒性におけるアミロイドβコンホマーの役割2015

    • Author(s)
      泉尾 直孝、村上 一馬、久米 利明、前田 雅弘、入江 一浩、清水 孝彦
    • Journal Title

      基礎老化研究

      Volume: 39 Pages: 29-34

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 脳特異的Superoxide dismutase 2欠損マウスはスポンジ状脳症を誘導する2018

    • Author(s)
      泉尾 直孝、野田 義博、清水 孝彦
    • Organizer
      第138回日本薬理学会関東部会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 青ジソに含まれるアミロイドβ42の凝集阻害物質の作用機構とマウスにおける生体内代謝2018

    • Author(s)
      坂口 嘉紀、村上 一馬,花木 瑞穂,泉尾 直孝,小澤 裕介,粟野 達也,高部 圭司,川瀬 泰司, 廣瀬 賢治,三羽 伸明,久米 利明,清水 孝彦,入江 一浩
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Systemic insulin resistance induces cognitive and psychiatric symptoms in Alzheimer’s disease model mice2018

    • Author(s)
      Izuo N, Watanabe N, Noda Y, Saito T, Saido T, Hotta H, Shimizu T
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アミロイドbeta「毒性コンホマー」を標的にしたアルツハイマー病の治療・診断法の開発2017

    • Author(s)
      泉尾直孝, 久米利明, 村上一馬, 徳田隆彦, 前田雅弘, 入江一浩, 清水孝彦
    • Organizer
      第137回日本薬学会年会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Brain-specific superoxide dismutase 2 deficiency induces neurodegeneration in mice2017

    • Author(s)
      Naotaka Izuo, Yoshihiro Noda, Takahiko Shimizu
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール(長崎県長崎市)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report
  • [Presentation] Docosahexaenoic acid is a potent anti-inflammatory mediator in microglia2017

    • Author(s)
      Izuo Naotaka, Kasahara Chihiro, Yamamoto Yuka, Shimizu Takahiko
    • Organizer
      第40回日本基礎老化学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 全身性のインスリン抵抗性は老人斑非依存的にアルツハイマー病モデルマウスに行動異常を誘導する2017

    • Author(s)
      泉尾 直孝、笠原 千尋、村上 一馬、入江 一浩、清水 孝彦
    • Organizer
      生体機能と創薬シンポジウム2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] 全身性インスリン抵抗性はアルツハイマー病モデルマウスに行動異常を誘導する2017

    • Author(s)
      泉尾 直孝、笠原 千尋、村上 一馬、入江 一浩、清水 孝彦
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脳特異的Superoxide dismutase 2欠損マウスは神経変性を誘導する2016

    • Author(s)
      泉尾直孝、野田義博、清水孝彦
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] オメガ-3脂肪酸はミクログリアの活性化を調節する2016

    • Author(s)
      笠原千尋、泉尾直孝、横手幸太郎、清水孝彦
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Identification of the “toxic conformer” of amyloid beta and its pathogenic contribution of Alzheimer’s disease2016

    • Author(s)
      Naotaka Izuo, Kazuma Murakami, Toshiaki Kume, Masahiro Maeda, Kazuhiro Irie, Takahiko Shimizu
    • Organizer
      2016 Spring International Conference of the Korean Society for Gerontology
    • Place of Presentation
      Hotel Laonzena(韓国テグ)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Abeta42の22-23位におけるターン構造はAbeta42誘発神経毒性を調節する2016

    • Author(s)
      泉尾直孝、久米利明、村上一馬、前田雅弘、入江一浩、清水孝彦
    • Organizer
      第39回日本基礎老化学会大会
    • Place of Presentation
      伊勢原市民文化会館(神奈川県伊勢原市)
    • Year and Date
      2016-05-27
    • Related Report
      2016 Research-status Report
  • [Presentation] アミロイド β の毒性コンホマーにきわめて特異的な抗体の開発とアルツハイマー病診断への応用2016

    • Author(s)
      村上一馬, 徳田真樹, 鈴木天志, 入江由美, 花木瑞穂, 柳田 亮, 物部容子, 赤木謙一, 石井亮太郎, 建部 陽嗣, 徳田隆彦, 前田雅弘, 久米利明, 泉尾直孝, 清水孝彦, 入江一浩
    • Organizer
      日本農芸化学大会2016年度大会
    • Place of Presentation
      札幌コンベンションセンター (北海道札幌市)
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] Passive immunization with the toxic conformer of Aβ; ameliorated behavioral abnormalities in Alzheimer’s-like model without affecting senile plaque deposition2016

    • Author(s)
      Naotaka Izuo, Kazuma Murakami, Toshiaki Kume, Kazuhiro Irie, Koutaro Yokote, Takahiko Shimizu
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
  • [Presentation] Characterization of the monoclonal antibody (24B3) highly recognizing the toxic turn of amyloid β42 and its application to diagnosis for Alzheimer’s disease2016

    • Author(s)
      Kazuma Murakami, Mizuho Hanaki, Ken-ichi Akagi, Ryotaro Ishii, Harutsugu Tatebe, Takahiro Tokuda, Masahiro Maeda, Naotaka Izuo, Takahiko Shimizu and Kazuhiro Irie
    • Organizer
      第8回武田薬科学シンポジウム
    • Place of Presentation
      武田薬品研修所 (大阪府吹田市)
    • Year and Date
      2016-01-21
    • Related Report
      2015 Research-status Report
  • [Presentation] Characterization of monoclonal antibodies against the toxic turn of amyloid β42 and their application to diagnosis for Alzheimer’s disease2015

    • Author(s)
      Murakami, Kazuma; Hanaki-Sato, Mizuho; Moro, Maria L; Giaccone, Giorgio; Tagliavini, Fabrizio; Akagi, Ken-ichi; Ishii, Ryotaro; Tokuda, Takahiko; Maeda, Masahiro; Izuo, Naotaka; Shimizu, Takahiko; Irie, Kazuhiro
    • Organizer
      International Chemical Congress of Pacific Basin Societies 2015
    • Place of Presentation
      Hawaii Convention Center, ホノルル (アメリカ)
    • Year and Date
      2015-12-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Aβ毒性コンホマーの選択的除去は老人斑形成を阻害せずにアルツハイマー病モデルマウスの行動異常を改善する2015

    • Author(s)
      泉尾直孝、村上一馬、前田雅弘、久米利明、横手幸太郎、入江一浩、清水孝彦
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド (兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Insulin receptor mutation results in insulin resistance but does not alter lifespan or Alzheimer’s-like phenotype in mice2015

    • Author(s)
      Naotaka Izuo, Kazuma Murakami, Kazuhiro Irie, Takuji Shirasawa, Koutaro Yokote and Takahiko Shimizu
    • Organizer
      Keystone symposia
    • Place of Presentation
      京都ウエスティン都ホテル (京都府京都市)
    • Year and Date
      2015-10-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Aβ毒性コンホマーの選択的除去は老人班に影響せずアルツハイマー病症状を改善する2015

    • Author(s)
      泉尾直孝、村上一馬、前田雅弘、久米利明、横手幸太郎、入江一浩、清水孝彦
    • Organizer
      第34回 日本認知症学会学術集会
    • Place of Presentation
      リンクステーションホール青森 (青森県青森市)
    • Year and Date
      2015-10-02
    • Related Report
      2015 Research-status Report
  • [Presentation] Aβ毒性コンホマーの選択的除去は老人班非依存的にアルツハイマー病モデルマウスの行動異常を改善する2015

    • Author(s)
      泉尾直孝, 村上一馬, 前田雅弘, 久米利明, 横手幸太郎, 入江一浩, 清水孝彦
    • Organizer
      認知症研究を知る若手研究者の集まり 2015
    • Place of Presentation
      ニューサンピア高崎 (群馬県高崎市)
    • Year and Date
      2015-08-01
    • Related Report
      2015 Research-status Report
  • [Presentation] アミロイドβの「毒性コンホマー」を標的とした受動免疫療法はアルツハイマー病モデルの神経症状を改善する2015

    • Author(s)
      泉尾直孝、村上一馬、久米利明、赤池昭紀、白澤卓二、横手幸太郎、入江一浩、清水孝彦
    • Organizer
      第38回日本基礎老化学会
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Year and Date
      2015-06-12
    • Related Report
      2015 Research-status Report
  • [Remarks] 千葉大学医学部先進加齢医学のHP

    • URL

      http://www.m.chiba-u.jp/class/clin-cellbiol/research/contents/increasing_age.html#jump1

    • Related Report
      2016 Research-status Report

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Published: 2015-04-16   Modified: 2019-12-27  

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