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Roles of neural metabolic signaling pathway in transitional mechanism to AD

Research Project

Project/Area Number 17H02188
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied health science
Research InstitutionNational Center for Geriatrics and Gerontology

Principal Investigator

Akiko Taguchi  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, 部長 (80517186)

Co-Investigator(Kenkyū-buntansha) 福井 裕介  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)
田之頭 大輔  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 (80724575)
王 蔚  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 (00845167)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywords糖尿病 / 糖代謝調節 / 脳 / 認知機能 / 加齢 / 糖代謝調節経路 / アルツハイマー病 / 脳代謝調節経路 / 認知機能障害 / インスリンシグナル / 認知症 / 栄養 / 運動 / 老化 / インスリン受容体基質 / 代謝 / 痴呆 / 脳神経疾患 / トランスレーショナルリサーチ
Outline of Final Research Achievements

We found that1) type2 diabetes (T2DM)-induced memory decline accompanied by alterations in glucose metabolism-related signaling components in the hippocampus is provoked by an amyloid beta (Aβ)-independent mechanism, 2) type1 diabetes (T1DM)-induced memory deficit arises independently of the modification of glucose metabolism-related signaling factors and independently of Aβ, 3) hippocampal alterations in glucose metabolism-related signaling occur when middle-aged novel AD model mice show cognitive decline, 4) T2DM additively exacerbates cognitive impairment and alterations in hippocampal glucose metabolism-related signaling in middle-aged novel AD model mice, and 5) aged mice that have normal glucose metabolism display Aβ-unrelated memory impairment accompanied by alterations in hippocampal glucose metabolism-related signaling as well as T2DM model mice show.

Academic Significance and Societal Importance of the Research Achievements

本研究は、脳の糖代謝調節経路とAβ非依存的認知機能低下の関係および同経路とAβの関係を明らかにした点で学術的意義が深い。これらの詳細なメカニズムについての今後の検討により、認知機能障害の新たな予防・治療法の開発に貢献する可能性がある。

Report

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

    (48 results)

All 2020 2019 2018 2017

All Journal Article (17 results) (of which Peer Reviewed: 16 results,  Open Access: 4 results) Presentation (31 results) (of which Int'l Joint Research: 9 results,  Invited: 9 results)

  • [Journal Article] 代謝・神経機能障害と脳内インスリンシグナル;The relations between neural insulin signaling and metabolic and neural dysfunctions2019

    • Author(s)
      田口明子
    • Journal Title

      日本老年医学会誌

      Volume: 56 Pages: 234-240

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of insulin receptor substrates in cognitive impairment and Alzheimer's disease.2019

    • Author(s)
      Tanokashira D, Fukuokaya W, Taguchi A.
    • Journal Title

      Neural Regen Res.

      Volume: Volume 14, Issue 8 Issue: 8 Pages: 1330-1334

    • DOI

      10.4103/1673-5374.253535

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [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] 脳インスリンシグナルと認知機能障害2018

    • Author(s)
      田口明子
    • Journal Title

      医療の広場

      Volume: 58 (5) Pages: 4-6

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Metformin treatment am,eliorates diabetes-associated decline in hippocampal neurogenesis and memory via phosphorylation of insulin receptor substrate 12018

    • Author(s)
      Tanokashira D , Kurata E, Fukuokaya W, Kawabe K, Takeuchi H, Kashiwada M, Nakazato M, Taguchi A
    • Journal Title

      FEBS Open Bio.

      Volume: 18;8(7) Issue: 7 Pages: 1104-1118

    • DOI

      10.1002/2211-5463.12436

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 model2018

    • 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

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuroprotective Effects of Tocovid Pretreatment in a Mouse Stroke Model2018

    • Author(s)
      Jiao Y, Shang J, Ohta Y, Yan H, 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: 2166-2174

    • DOI

      10.1016/j.jstrokecerebrovasdis.2018.03.014

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antineuroinflammatory Effect of SMTP-7 in Ischemic Mice2018

    • Author(s)
      Huang Y, Ohta Y, Shang J, Morihara R, Nakano Y, Fukui Y, Liu X, Shi X, Feng T, Yamashita T, Sato K, Takemoto M, Hishikawa N, Suzuki E, Hasumi K, Abe K
    • Journal Title

      J Stroke Cerebrovasc Dis.

      Volume: 27(11) Pages: 3084-3094

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protective effect of a novel sigma-1 receptor agonist is associated with reduced endoplasmic reticulum stress in stroke male mice2018

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

      J Neurosci Res.

      Volume: 96(10) Issue: 10 Pages: 1707-1716

    • DOI

      10.1002/jnr.24270

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuroprotective effects of SMTP-44D in mice stroke model in relation to neurovascular unit and trophic coupling2018

    • Author(s)
      Shi X, Ohta Y, Shang J, Morihara R, Nakano Y, Fukui Y, Liu X, Feng T, Huang Y, Sato K, Takemoto M, Hishikawa N, Yamashita T, Suzuki E, Hasumi K, Abe K
    • Journal Title

      J Neurosci Res.

      Volume: 96(12) Issue: 12 Pages: 1887-1899

    • DOI

      10.1002/jnr.24326

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 高齢者糖尿病におけるアルツハイマー病の発症機構と病態特性:脳インスリンシグナル関与の可能性2018

    • Author(s)
      田口明子、櫻井 孝
    • Journal Title

      月刊 糖尿病

      Volume: 112, 10(7) Pages: 38-42

    • 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
  • [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] 糖尿病治療薬アクトスの認知症への応用2017

    • Author(s)
      田之頭大輔、田口明子
    • Journal Title

      Medical Science Digest.

      Volume: 43(10) Pages: 2-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] Modification of hippocampal IRS1 via Serine Phosphorylation Correlates with Aβ-Unrelated Memory Deficits2020

    • Author(s)
      Wei Wang, Daisuke Tanokashira, Yusuke Fukui, Megumi Maruyama, Chiemi Kuroiwa, Takashi Saito, Takaomi C.Saido and Akiko Taguchi
    • Organizer
      Adult Neurogenesis Meeting 2020, Sendai, Japan
    • Related Report
      2019 Annual Research Report
  • [Presentation] Metformin enhances adult neurogenesis and memory function through hippocampal IRS1 signaling independent of the hypoglycemic effect2019

    • Author(s)
      Akiko Taguchi
    • Organizer
      10th World Gene Convention. Qingdao, China
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Antidiabetic medication enhances neurogenesis and memory function via hippocampal insulin signaling2019

    • Author(s)
      Akiko Taguchi
    • Organizer
      2019 International Conference on Biotechnology and Bioengineering. Poznan, Poland
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Metformin enhances neurogenesis and memory function via hippocampal insulin signaling independent of the hypoglycemic effect2019

    • Author(s)
      Akiko Taguchi
    • Organizer
      8th Annual World Congress of Advanced Materials. Osaka, Japan
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Metformin enhances neurogenesis and memory function via hippocampal insulin signaling independent of the hypoglycemic effect2019

    • Author(s)
      Akiko Taguchi
    • Organizer
      17th Annual Congress of International Drug Discovery Science and Technology. Kyoto, Japan
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Phosphorylation of specific serine sites on hippocampal insulin receptor substrate 1 is associated with Alzheimer's disease-unrelated memory deficit and -related pathology2019

    • Author(s)
      Daisuke Tanokashira, Yusuke Fukui, Wei Wang, Megumi Maruyama, Chiemi Kuroiwa, Takashi Saito, Takaomi C. Saido, Akiko Taguchi
    • Organizer
      Society for Neuroscience 2019, Chicago, USA
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アミロイドβ関連/非関連認知機能低下と脳インスリンシグナル ―― 認知症発症既存仮説 vs.多様な潜在的機構 ――2019

    • Author(s)
      田口明子
    • Organizer
      第2回B6J Aged研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 糖代謝変容と高次脳機能障害を結ぶ潜在的経路としての脳インスリンシグナルの役割2019

    • Author(s)
      田口明子
    • Organizer
      第11回Stroke Science Academy, 福岡市、日本
    • Related Report
      2019 Annual Research Report
    • Invited
  • [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 東京、日本
    • 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 東京、日本
    • 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 大阪、日本
    • 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 大阪、日本
    • Related Report
      2019 Annual Research Report
  • [Presentation] 2型糖尿病による海馬IRSシグナルの変化とアルツハイマー病態増悪化との連関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38回日本認知症学会 東京、日本
    • Related Report
      2019 Annual Research Report
  • [Presentation] 認知機能低下における海馬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42回日本分子生物学会 福岡市、日本
    • Related Report
      2019 Annual Research Report
  • [Presentation] 海馬IRSシグナルを介した糖尿病によるアルツハイマー病増悪化機構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・肥満動物学会, 群馬県高崎市, 日本
    • Related Report
      2019 Annual Research Report
  • [Presentation] 認知機能低下におけるセリンリン酸化を介した海馬IRS1シグナルの変化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・肥満動物学会, 群馬県高崎市, 日本
    • Related Report
      2019 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] 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] メトフォルミンが海馬依存的認知機能へ与える影響についての検討.2018

    • Author(s)
      今井萌乃、田之頭大輔、倉田栄子、福岡屋航、柏田舞波、中里雅光、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、田口明子.
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 糖尿病と認知症を結ぶ潜在的経路としての脳インスリンシグナルの機能.2017

    • Author(s)
      田口明子.
    • Organizer
      第30回日本老年学会総会、第59回日本老年医学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 糖尿病関連疾患として捉える認知症の誘導機構における脳インスリンシグナルの関与.2017

    • Author(s)
      田口明子.
    • Organizer
      関西医科大学Diabetes Research Forum
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Neural insulin signaling correlates with diabetes-related cognitive impairment.2017

    • Author(s)
      Daisuke Tanokashira, Wataru Fukuokaya, Akinori Tokunaga, Tamiko Saji, Eiko Kurata, and Akiko Taguchi.
    • Organizer
      Cell Symposia-Metabolic Disease Therapies
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Altered neural insulin signaling correlates with both age and diabetes-related cognitive impairment.2017

    • Author(s)
      Akiko Taguchi.
    • Organizer
      The International Symposium on Dementia 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Analysis of synaptic insulin signaling in the hippocampus and prefrontal cortex in diabetes-associated cognitive impairment.2017

    • Author(s)
      Tada H, Tokunaga A, Tanokashira D, Kashiwada M, Saji T, Imai M, Taguchi A.
    • Organizer
      Society for Neuroscience
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mechanisms linking between impaired hippocampal insulin signaling and diabetes-associated cognitive dysfunction.2017

    • Author(s)
      Tokunaga A, Tada H, Tanokashira D, Saji T, Kashiwada M, Taguchi A.
    • Organizer
      Society for Neuroscience
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [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
  • [Presentation] 糖尿病モデル動物を用いた認知機能障害発症機序の解析.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] 神経細胞新生に対する糖尿病薬の効果についての検討 The effect of diabetes drug on adult hippocampal neurogenesis.2017

    • Author(s)
      田之頭大輔、福岡屋航、倉田栄子、中里雅光、田口明子.
    • Organizer
      第13回成体脳のニューロン新生懇談会
    • 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

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Published: 2017-04-28   Modified: 2023-12-25  

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