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Analysis of synaptic insulin signaling in the hippocampus and prefrontal cortex in diabetes-associated cognitive impairment.

Research Project

Project/Area Number 17H05062
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Environmental physiology(including physical medicine and nutritional physiology)
Research InstitutionYokohama City University (2020)
National Center for Geriatrics and Gerontology (2017-2019)

Principal Investigator

TADA Hirobumi  横浜市立大学, 医学研究科, 特任准教授 (20464993)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥24,570,000 (Direct Cost: ¥18,900,000、Indirect Cost: ¥5,670,000)
Fiscal Year 2020: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
Keywords糖代謝シグナル / 認知機能障害 / 認知機能 / シナプス可塑性 / 易怒性攻撃行動 / 加齢 / シナプス / 認知症中核症状 / 認知症周辺症状 / 認知症 / 糖尿病 / インスリンシグナル / インスリン受容体基質
Outline of Final Research Achievements

Synaptic dysfunction is thought to be an early intracerebral change that occurs before brain atrophy during the pathological progression of dementia. Recent large-scale epidemiological studies have shown risk factors that influence the progression of dementia. Disruption of biological homeostasis by aging and abnormal glucose metabolism is the greatest risk factor for dementia, and its relationship with synaptic function has been considered to be important. In this study, we investigated that disregulation of synaptic insulin signaling affects neuronal plasticity in hippocampus and medial prefrontal cortex involved in dementia like behaviors.

Academic Significance and Societal Importance of the Research Achievements

超高齢化社会と呼ばれる現代において、健康長寿の延伸が重要視されている。高齢者の15%を占める認知症の改善は、健康長寿社会実現に欠かすことができない要因である。また団塊の世代が75歳を迎える4年後は2025年問題として、社会全体の対応策が求められている。このように認知症に対して効果的な治療方法が望まれている一方で、現状では最も治療効果が得られていない疾患領域の一つとして捉えられている。シナプスを起点とする糖代謝シグナルを標的とする本研究は、新しい側面からの認知症病態メカニズム解明につながることが期待できる。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (30 results)

All 2020 2019 2018 2017 Other

All Journal Article (4 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (24 results) (of which Int'l Joint Research: 6 results,  Invited: 8 results) Remarks (2 results)

  • [Journal Article] 内分泌系の加齢変化と脳認知機能2020

    • Author(s)
      多田敬典
    • Journal Title

      老年内科

      Volume: 2 Pages: 672-679

    • Related Report
      2020 Annual Research Report
  • [Journal Article] CRMP2-binding compound, edonerpic maleate, accelerates motor function recovery from brain damage2018

    • Author(s)
      Abe Hiroki、Jitsuki Susumu、Nakajima Waki、Murata Yumi、Jitsuki-Takahashi Aoi、Katsuno Yuki、Tada Hirobumi、Sano Akane、Suyama Kumiko、Mochizuki Nobuyuki、Komori Takashi、Masuyama Hitoshi、Okuda Tomohiro、Goshima Yoshio、Higo Noriyuki、Takahashi Takuya
    • Journal Title

      Science

      Volume: 360 Issue: 6384 Pages: 50-57

    • DOI

      10.1126/science.aao2300

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Social isolation suppresses actin dynamics and synaptic plasticity through ADF/cofilin inactivation in the developing rat barrel cortex2017

    • Author(s)
      Tada H, Miyazaki T, Takemoto K, Jitsuki S, Nakajima W, Koide M, Yamamoto N, Taguchi A, Kawai H, Komiya K, Suyama K, Abe H, Sano A, Takahashi T.
    • Journal Title

      Sci. Rep

      Volume: 7 Issue: 1 Pages: 8471-8471

    • DOI

      10.1038/s41598-017-08849-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optical inactivation of synaptic AMPA receptors erases fear memory.2017

    • Author(s)
      K. Takemoto, H. Iwanari, H. Tada, K. Suyama, A. Sano, T. Nagai, T. Hamakubo, T. Takahashi
    • Journal Title

      Nat Biotechnol

      Volume: 35 Issue: 1 Pages: 38-47

    • DOI

      10.1038/nbt.3710

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Age-related glucocorticoid endocrinological regulation involved in social cognitive function2020

    • Author(s)
      Hirobumi TADA
    • Organizer
      AOCE-SICEM 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 精神神経疾患における攻撃性制御の意義と分子機序の解明2020

    • Author(s)
      多田敬典
    • Organizer
      第163回日本獣医学会学術集会 日本比較薬理学・毒性学会シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 加齢に伴うストレス内分泌変化が脳認知機能に及ぼす影響2020

    • Author(s)
      多田敬典
    • Organizer
      第62回日本老年医学会学術集会「エイジングサイエンスフォーラム~最新老化研究から新しい健康概念へ」
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 露地栽培アガリクス(KA21株)の加齢性運動機能低下に対する効果の検討2020

    • Author(s)
      多田敬典, 元井章智, 元井里奈, 赤木一考
    • Organizer
      第20回日本抗加齢医学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 露地栽培アガリクス(KA21株)の寿命、筋・神経系に対する効果の検討2020

    • Author(s)
      多田敬典, 元井章智, 元井里奈, 赤木一考
    • Organizer
      第100回日本獣医麻酔外科学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Paramylon, a β-1,3-Glucan from Euglena gracilis, extends lifespan and diminishes age-related neuromuscular decline.2020

    • Author(s)
      Tada H, Yasuda K, Nakashima A, Suzuki K, Tokunaga A, Akagi K.
    • Organizer
      第43回日本基礎老化学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 慢性ストレス環境に伴う社会的行動障害誘導機構の解明2020

    • Author(s)
      多田敬典、高橋琢哉
    • Organizer
      第93回薬理学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 生活環境による内分泌変化が脳認知機能に及ぼす影響2020

    • Author(s)
      多田敬典
    • Organizer
      第40回日本基礎老化学会シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 精神神経疾患における攻撃性制御の意義と分子機序の解明2019

    • Author(s)
      多田敬典
    • Organizer
      第31回日本行動神経内分泌研究会 攻撃行動シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Chronic stress environment causes social cognitive impairment and excessive aggression by altering synaptic plasticity in rat medial prefrontal cortex.2019

    • Author(s)
      Hirobumi TADA
    • Organizer
      35th Spring International Conference of the Korean Society for Gerontology and Korea-Japan Joint Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Chronic stress causes excessive aggression by altering synaptic actin dynamics in the mPFC.2019

    • Author(s)
      Hirobumi TADA, Takuya Takahashi
    • Organizer
      第42回日本基礎老化学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Chronic stress causes excessive aggression by altering synaptic actin dynamics in the mPFC.2019

    • Author(s)
      Hirobumi Tada, Takuya Takahashi
    • Organizer
      9th FAOPS
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Chronic stress environment causes social cognitive impairment and excessive aggression by altering synaptic plasticity in rat medial prefrontal cortex.2018

    • Author(s)
      Hirobumi Tada
    • Organizer
      4th NCGG-ICAH
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Chronic stress environment causes social cognitive impairment and excessive aggression by altering synaptic AMPA receptor delivery in rat medial prefrontal cortex.2018

    • Author(s)
      Hirobumi Tada
    • Organizer
      第41回日本基礎老化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 糖尿病に伴う脳内糖代謝シグナル活性異常を介したシナプスを起点とする認知機能障害誘導メカニズムの解析2018

    • Author(s)
      多田敬典、徳永暁憲、田之頭大輔、柏田舞波、佐治多美子、今井萌乃、田口明子
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 糖尿病モデル動物を用いた認知機能障害発症機構の解析2018

    • Author(s)
      徳永暁憲、多田敬典、田之頭大輔、佐治多美子、柏田舞波、竹井喜美、佐藤駿介、斉藤貴志、西道隆臣、田口明子
    • Organizer
      第32回日本糖尿病肥満動物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 糖尿病によるアルツハイマー病態増悪化メカニズムの検討2018

    • Author(s)
      田之頭大輔、徳永暁憲、多田敬典、佐治多美子、柏田舞波、竹井喜美、佐藤駿介、斉藤貴志、西道隆臣、田口明子
    • Organizer
      第32回日本糖尿病肥満動物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Analysis of synaptic insulin signaling in the hippocampus and prefrontal cortex in diabetes-associated cognitive impairment.2017

    • Author(s)
      Hirobumi Tada, Akinori Tokunaga, Daisuke Tanokashira, Mana Kashiwada, Tamiko Saji, Moeno Imai, Akiko Taguchi
    • Organizer
      Neuroscience 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mechanisms linking impaired hippocampal insulin signaling and diabetes-associated cognitive dysfunction.2017

    • Author(s)
      Akinori Tokunaga, Hirobumi Tada, Daisuke Tanokashira, Tamiko Saji, Mana Kashiwada, Moeno Imai, Akiko Taguchi
    • Organizer
      Neuroscience 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mechanisms of cognitive impairment induced by altering the insulin-like signaling in the hippocampus and prefrontal cortex of diabetic model mice.2017

    • Author(s)
      多田敬典、徳永暁憲、田之頭大輔、佐治多美子、柏田舞波、田口明子
    • Organizer
      第40回神経科学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 糖尿病に伴う脳インスリン様シグナル変容がアルツハイマー病態に与える影響2017

    • Author(s)
      田之頭大輔、徳永暁憲、多田敬典、佐治多美子、柏田舞波、竹井喜美、斉藤貴志、西道隆臣、田口明子
    • Organizer
      第36回認知症学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 糖尿病による脳インスリン様シグナルを介したアルツハイマー病態増悪化機構の検討2017

    • Author(s)
      田之頭大輔、徳永暁憲、多田敬典、佐治多美子、柏田舞波、竹井喜美、斉藤貴志、西道隆臣、田口明子
    • Organizer
      第32回日本糖尿病合併症学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 糖尿病モデル動物を用いた認知機能障害発症喜寿尾の解析2017

    • Author(s)
      徳永暁憲、多田敬典、田之頭大輔、佐治多美子、柏田舞波, 田口明子
    • Organizer
      第26回海馬と高次脳機能学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 糖尿病に付随する脳インスリンシグナルの変容 がアルツハイマー病態に与える影響2017

    • Author(s)
      田之頭大輔、徳永暁憲、多田敬典、佐治多美子、柏田舞波、竹井喜美、佐藤駿介、斉藤貴志、西道隆臣、田口明子
    • Organizer
      第26回海馬と高次脳機能学会
    • Related Report
      2017 Annual Research Report
  • [Remarks] Researchmap 多田敬典

    • URL

      https://researchmap.jp/k10

    • Related Report
      2019 Annual Research Report
  • [Remarks] Researchmap 多田敬典

    • URL

      https://researchmap.jp/k10/

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report

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Published: 2017-04-28   Modified: 2022-01-27  

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