• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Mechanism for Brain Aging

Planned Research

Project AreaPrinciples of memory dynamism elucidated from a diversity of learning systems
Project/Area Number 25115004
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

Hisatsune Tatsuhiro  東京大学, 大学院新領域創成科学研究科, 准教授 (10238298)

Project Period (FY) 2013-06-28 – 2018-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥89,700,000 (Direct Cost: ¥69,000,000、Indirect Cost: ¥20,700,000)
Fiscal Year 2017: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2016: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2015: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2014: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
Fiscal Year 2013: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Keywords学習記憶 / 脳老化 / 海馬 / 報酬系 / ドーパミン / fMRI / 記憶 / 学習 / 認知症 / 学習・記憶 / アルツハイマー病 / タスクfMRI / 加齢
Outline of Final Research Achievements

In order to elucidate the mechanism of brain aging, we conducted a study using Alzheimer's disease model mice and a study for healthy elderly people. We found that the inflammatory response in brain tissue greatly contributes to the decline in brain function due to aging. When an inflammatory reaction occurs in the brain, production of inflammatory cytokines is enhanced in glial cells (astrocytes and microglia), and the function of the cerebrovascular barrier is reduced in cerebral blood vessels. It was found that such changes reduce synaptic function in each neuron, modulate the neural network, and reduce memory function and cognitive function during aging. In order to investigate the decline mechanism of learning and memory function, we performed operant learning task fMRI study to visualize brain circuit activity of mouse, such as Alzheimer's Disease model mice.

Academic Significance and Societal Importance of the Research Achievements

健康な人であっても高齢になれば、年とともに記憶機能や認知機能が低下する。神経炎症を、薬剤などで制御し抑制することによって、低下した脳機能を回復させることが可能であることが判った。通常のマウスに比べて、アルツハイマー病モデルマウスでは、海馬や報酬系の脳活動が変化していることが示唆された。オペラントタスクfMRI研究は、脳機能の低下メカニズムを調べ、記憶ダイナミズムを明らかにすることに加えて、意識や情動の面を含めた脳の全体的な認知機能を調べる上で重要な研究ツールになると期待された。

Report

(6 results)
  • 2018 Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (32 results)

All 2019 2018 2017 2016 2015 2013 Other

All Int'l Joint Research (7 results) Journal Article (12 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 12 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Remarks (5 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] 成均館大学(韓国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Imperial College London(英国)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] University of Bialystok(Lithuania)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Kaohsiung Medical University(Taiwan)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Imperial College London(英国)

    • Related Report
      2014 Annual Research Report
  • [Int'l Joint Research] University of Bialystok(Lithuania)

    • Related Report
      2014 Annual Research Report
  • [Int'l Joint Research] Kaohsiung Medical University(Taiwan)

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Elevated activation of a murine limbic network during cue-reward association learning revealed in 15.2 T fMRI.2019

    • Author(s)
      Sakurai, K., Ando, S., Takahashi, C., Shintani, T., Jung, W., Anh, D.T.N., Lee, C., Kim, Y, Kim S.-G., Hisatsune, T.
    • Journal Title

      Proc. Intl. Soc. Mag. Reson. Med.

      Volume: 27 Pages: 964-964

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hyperactivity of hippocampus-amygdala network during cue-reward association learning of APP/PS1 Alzheimer’s disease model mice detected by 14T-fMRI.2019

    • Author(s)
      Sakurai, K., Shintani, T., Hisatsune, T.
    • Journal Title

      Proc. Intl. Soc. Mag. Reson. Med.

      Volume: 27 Pages: 4467-4467

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] アルツハイマー病における神経炎症の関与2019

    • Author(s)
      久恒辰博
    • Journal Title

      細胞(ニューサイエンス社)

      Volume: 51 Pages: 44-46

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anserine/carnosine supplementation preserves blood flow in the prefrontal brain of elderly people carrying APOE e4.2018

    • Author(s)
      Ding, Q., Tanigawa, K., Kaneko, J., Totsuka, M., Katakura Y., Imabayashi, E., Matsuda, H., Hisatsune, T.
    • Journal Title

      Aging and Disease

      Volume: 9 Issue: 5 Pages: 334-345

    • DOI

      10.14336/ad.2017.0130

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Field-Map Distortion Correction on Resting State Functional Connectivity MRI2017

    • Author(s)
      Togo Hiroki、Rokicki Jaroslav、Yoshinaga Kenji、Hisatsune Tatsuhiro、Matsuda Hiroshi、Haga Nobuhiko、Hanakawa Takashi
    • Journal Title

      Front Neurosci

      Volume: 11 Pages: 656-656

    • DOI

      10.3389/fnins.2017.00656

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anserine/Carnosine Supplementation Suppresses the Expression of the Inflammatory Chemokine CCL24 in Peripheral Blood Mononuclear Cells from Elderly People2017

    • Author(s)
      Katakura, Y., Totsuka, M., Imabayashi, E., Matsuda, H., Hisatsune, T.
    • Journal Title

      Nutrients

      Volume: 9 Issue: 1 Pages: 1199-1199

    • DOI

      10.1038/s41598-017-13972-2

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anserine (beta-alanyl-3-methyl-L-histidine) improves neurovascular-unit dysfunction and spatial memory in aged AβPPswe/PSEN1dE9 Alzheimer’s-model mice.2017

    • Author(s)
      Kaneko, J., Enya, A., Enomoto, K., Ding, Q., Hisatsune, T.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 12571-12571

    • DOI

      10.1038/s41598-017-12785-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cholinergic modification of neurogenesis and gliosis improves the memory of AβPPswe/PSEN1dE9 Alzheimer’s model mice fed a high-fat diet.2017

    • Author(s)
      Matsuda, T., Hisatsune, T.
    • Journal Title

      Journal of Alzheimer’s Disease

      Volume: 56 Issue: 1 Pages: 1-23

    • DOI

      10.3233/jad-160761

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mouse BOLD fMRI imaging during operant learning at ultra-high field2017

    • Author(s)
      Jomura, N., Shintani, T., Sakurai, K., Kaneko, J., Hisatsune, T.
    • Journal Title

      Proc. Intl. Soc. Mag. Reson. Med.

      Volume: 25 Pages: 5365-5365

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of Anserine/Carnosine Supplementation on Verbal Episodic Memory in Elderly People2016

    • Author(s)
      Tatsuhiro Hisatsune, Jun Kaneko, Hiroki Kurashige, Yuan Cao, Hideo Satsu,
    • Journal Title

      Journal of Alzheimer’s Disease

      Volume: 50 Issue: 1 Pages: 149-159

    • DOI

      10.3233/jad-150767

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Daily Carnosine and Anserine Supplementation Alters Verbal Episodic Memory and Resting State Network Connectivity in Healthy Elderly Adults2015

    • Author(s)
      Jaroslav Rokicki, Lucia Li, Etsuko Imabayashi, Jun Kaneko, Tatsuhiro Hisatsune and Hiroshi Matsuda
    • Journal Title

      Frontiers in Aging Neuroscience

      Volume: 7 Pages: 219-219

    • DOI

      10.3389/fnagi.2015.00219

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Contribution of the P2Y1 receptor to hippocampal neuroinflammation and cognitive decline in a rodent model of focal cerebral stroke2013

    • Author(s)
      Chin Y, Kishi M, Sekino M, Nakajo F, Abe Y, Ohsaki H, Kato F, Koizumi S, Gac het C, Hisatsune T
    • Journal Title

      Journal of Neuroinflammation

      Volume: 26 Issue: 1 Pages: 10-95

    • DOI

      10.1186/1742-2094-10-95

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Aging and Anti-Aging of Cognitive Functions2018

    • Author(s)
      Hisatsune T
    • Organizer
      21st US-Japan Cellular and Gene Therapy Conference Neurodegenerative Diseases: Biology, Cellular and Gene Therapy
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Memory recovery on anserine (beta-alanyl-3-methyl-L-histidine)-treated ApoE4+/+ knocked-in APPβswe/PSEN1dE9 Alzheimer’s disease model mice2018

    • Author(s)
      Cheng Lin, Jun Kaneko, Mami Tochigi, Chitose Yoshimine, Tatsuhiro Hisatsune
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Influence of suppressed dopamine secretion to goal-directed behavior of mice2018

    • Author(s)
      Kung Chun Kao, Naohiro Jomura, Tatsuhiro Hisatsune
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Impulsive disorder in Alzheimer’s disease model mice revealed by fMRI imaging during operant learning2018

    • Author(s)
      Keisuke Sakurai, Teppei Shintani, Tatsuhiro Hisatsune
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The role of hippocampal newborn neuron on cognitive flexibility2018

    • Author(s)
      Junya Koga, Sayumi Yokota, Kazumasa Z Tanaka, Thomas J McHugh, Tatsuhiro Hisatsune
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Neuroimaging of mouse executive functions by operant learning task fMRI2017

    • Author(s)
      Hisatsune T
    • Organizer
      Neuroimaging -from Molecules to Networks, Hot Topics in Molecular Imaging, Ecole de Physique des Houches
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 東京大学大学院 久恒研究室

    • URL

      http://park.itc.u-tokyo.ac.jp/hisatsune-lab/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 久恒研究室

    • URL

      http://park.itc.u-tokyo.ac.jp/hisatsune-lab/

    • Related Report
      2016 Annual Research Report
  • [Remarks] Hisatsune Lab

    • URL

      http://park.itc.u-tokyo.ac.jp/hisatsune-lab/enindex.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 東京大学大学院 新領域創成科学研究科 久恒研究室

    • URL

      http://park.itc.u-tokyo.ac.jp/hisatsune-lab/

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
  • [Remarks] Hisatsune Lab, GSFS, The University of Tokyo

    • URL

      http://park.itc.u-tokyo.ac.jp/hisatsune-lab/enindex.html

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
  • [Patent(Industrial Property Rights)] ペリサイトの変成を抑制する剤2017

    • Inventor(s)
      (5)久恒辰博、金子順
    • Industrial Property Rights Holder
      (5)久恒辰博、金子順
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-035823
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 特許権2017

    • Inventor(s)
      久恒辰博、金子順
    • Industrial Property Rights Holder
      東京大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-035823
    • Filing Date
      2017
    • Related Report
      2016 Annual Research Report

URL: 

Published: 2013-07-10   Modified: 2022-03-01  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi