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Evaluation of new generation translocator protein ligand efficacy in a mouse model of Alzheimer`s disease.

Research Project

Project/Area Number 26830038
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Nerve anatomy/Neuropathology
Research InstitutionNational Institute of Radiological Sciences

Principal Investigator

Barron Anna  国立研究開発法人放射線医学総合研究所, 分子イメージング研究センター, 研究員 (40725694)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsAlzheimer`s / Dementia / hormone replacement / translocator protein / nootropic / Alzheimer`s disease / neuroactive steroid / Neurosteroid / Cognition / Translocator protein
Outline of Final Research Achievements

Our previous work has demonstrated that ligands of the translocator protein (TSPO) are protective in a mouse model of Alzheimer`s disease. The purpose of this study was to characterize the potential suitability of three new generation TSPO ligands. We tested the ability of the new generation TSPO ligands to penetrate the brain of living mice, as well as their ability to bind TSPO in human brain sections. Next we assessed their effect on memory, anxiety and depression-related behaviors in mice. All three TSPO ligands improved memory function and one also reduced depression-related behavior. TSPO ligands are thought to improve memory by increasing brain hormone production. Confirming this mechanism of action, memory improvements in TSPO-ligand treated mice were blocked by inhibition of hormone production. Our findings indicate these new TSPO ligands may be promising therapeutic candidates for the treatment of Alzheimer`s disease.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (5 results)

All 2015

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Acknowledgement Compliant: 2 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Neurosteroidogenesis today: Novel targets for neurosteroid synthesis and action and their relevance for translational research2015

    • Author(s)
      Patrizia Porcu, Anna M Barron, Cheryl Frye, S-Y Yang, Roberto Cosimo Melcangi, GianCarlo Panzica
    • Journal Title

      Journal of Neuroendocrinology

      Volume: 28(2) Issue: 2 Pages: 1-19

    • DOI

      10.1111/jne.12351

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The Impact of Luteinizing hormone and Testosterone on beta amyloid (Aβ) accumulation: animal and human clinical studies2015

    • Author(s)
      [2]Verdile, G.V., Asih, P. Barron, A.M., Whajoepramono, E.J., Ittner, L.M., Martins, R.N.
    • Journal Title

      Hormones and Behavior

      Volume: 76 Pages: 81-90

    • DOI

      10.1016/j.yhbeh.2015.05.020

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] In vivo evaluation of the therapeutic potential of novel translocator protein ligands (TSPO) for the treatment of Alzheimer`s disease2015

    • Author(s)
      Asih, P. R., Ji, B., Katsifis, A., Mattner, F., Caruso, D., Melcangi, R.C., Higuchi, M., Martins, R.N., Barron, A.M.
    • Organizer
      Alzheimer`s Association International Conference
    • Place of Presentation
      Washington, USA
    • Year and Date
      2015-07-18 – 2015-07-23
    • Related Report
      2014 Research-status Report
  • [Presentation] In vivo evaluation of the therapeutic potential of novel translocator protein (TSPO) ligands for the treatment of Alzheimer's disease2015

    • Author(s)
      Asih, P.R., Bin, J., Katsifis, A., Mattner, F., Caruso, D., Melcangi, R.C., Higuchi, M., Martins, R.N., Barron, A.M.
    • Organizer
      Alzheimer`s Association International Conference
    • Place of Presentation
      Washington DC
    • Year and Date
      2015-07-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Translocator protein as a therapeutic target for Alzheimer`s disease2015

    • Author(s)
      Barron, A.M., Asih, P. R., Ji, B., Katsifis, A., Pike, C.J., Martins, R.N., Higuchi, M.
    • Organizer
      International Steroids and Nervous System
    • Place of Presentation
      Torino, Italy
    • Year and Date
      2015-02-14 – 2015-02-18
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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