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

Investigation of microglia and chronic stress in the onset of Parkinson disease

Research Project

Project/Area Number 15K06783
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionNippon Medical School

Principal Investigator

Sugama Shuei  日本医科大学, 医学部, 講師 (70302461)

Co-Investigator(Renkei-kenkyūsha) KAKINUMA Yoshihiko  日本医科大学, 大学院医学研究科, 教授 (40233944)
TAKENOUCHI Takato  国立筑波農業資源研究所, 主任研究員 (20292518)
HASHIMOTO Makoto  東京都神経科学総合研究所, 副参事研究員 (50189502)
Research Collaborator Conti Bruno  米国スクリップス医学研究所, 教授
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords慢性ストレス / パーキンソン病 / ミクログリア / ドーパミン / ノルアドレナリン / 黒質 / 青斑核 / 腹側被蓋野 / ストレス / 交感神経系 / 酸化ストレス / 視床下部 / 鬱病
Outline of Final Research Achievements

In this study, we investigated the effect of chronic stress and microglia in the onset of Parkinson disease. To the best of our knowledge, we report the first evidence that chronic restraint stress in the rat substantially reduces the nigral dopaminergic and locus coeruleus noradrenergic neuronal cells. This reduction was accompanied by robust microglial activation and oxidative stress, marked by nitrotyrosine in the midbrain. These results indicate that chronic stress may trigger the dopaminergic and noradrenergic neurodegeneration by virtue of increased oxidative stress, and that activated microglia, detected in the midbrain, may play an important role in modulating the neurotoxic effects of oxidative stress. Thus, our findings suggest that exposure to chronic stress itself may trigger the dopaminergic and noradrenergic neurodegeneration, a cause of Parkinson disease.

Report

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

    (13 results)

All 2018 2017 2016 2015

All Journal Article (10 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 10 results,  Open Access: 4 results,  Acknowledgement Compliant: 5 results) Presentation (3 results)

  • [Journal Article] Potential application of centrifuges to protect the CNS in space and on earth2018

    • Author(s)
      Hashimoto M, Ho G, Shimizu Y, Sugama S, Takenouchi T, Waragai M, Wei J, Takamatsu Y
    • Journal Title

      Curr Alzheimer Res

      Volume: 15 Issue: 6 Pages: 544-551

    • DOI

      10.2174/1567205015666171229225501

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Evolvability of amyloidogenic proteins in human brain2018

    • Author(s)
      Hashimoto M, Ho G, Sugama S, Takamatsu Y, Shimizu Y, Takenouchi T, Waragai M, Masliah E
    • Journal Title

      J Alzheimers Dis

      Volume: 62 Issue: 1 Pages: 73-83

    • DOI

      10.3233/jad-170894

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Lack of interleukin-13 receptor a1 delays the loss of dopaminergic neurons during chronic stress2017

    • Author(s)
      Mori S, Sugama S, Nguyen W, Michel T, Sanna MG, Sanchez-Alavez M, Cintron-Colon R, Moroncini G, Kakinuma Y, Maher P, Conti B
    • Journal Title

      J Neuroinflammation

      Volume: 14 Pages: 88-88

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Importance of adiponectin activity in the pathogenesis of Alzheimer's disease2017

    • Author(s)
      Waragai M, Ho G, Takamatsu Y, Sekiyama K, Sugama S, Takenouchi T, Masliah E, Hashimoto M
    • Journal Title

      Ann Clin Transl Neurol

      Volume: 4 Issue: 8 Pages: 591-600

    • DOI

      10.1002/acn3.436

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Letter to the Editor Re:"Reconsidering the role of glial cells in chronic stress-induced dopaminergic neurons loss within the substantia nigra? Friend of foe?" by Ong et al. Brain Behavior and Immunity, 2016.2017

    • Author(s)
      Sugama S, Kakinuma Y
    • Journal Title

      Brain Behav Immun

      Volume: 60 Pages: 383-383

    • DOI

      10.1016/j.bbi.2016.11.028

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Combined immunotherapy with “anti-insulin resistance” therapy as a novel therapeutic strategy against neurodegenerative diseases.2016

    • Author(s)
      Takamatsu Y, Ho G, Koike W, Sugama S, Takenouchi T, Waragai M, Wei J, Sekiyama K, Hashimoto M.
    • Journal Title

      npj Parkinson’s Disease

      Volume: 3 Issue: 1 Pages: 4-4

    • DOI

      10.1038/s41531-016-0001-1

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Non-neuronal cardiac cholinergic system influences CNS via the vagus nerve to acquire a stress-refractory propensity.2016

    • Author(s)
      Oikawa S, Kai Y, Tsuda M, Ohata H, Mano A, Mizoguchi N, Sugama S, Nemoto T, Suzuki K, Kurabayashi A, Muramoto K, Kaneda M, and Kakinuma Y.
    • Journal Title

      Clinical Science

      Volume: 130(21) Issue: 21 Pages: 1913-1928

    • DOI

      10.1042/cs20160277

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Loss of dopaminergic neurons occurs in the ventral tegmental area and hypothalamus of rats following chronic stress: Possible pathogenetic loci for depression involved in Parkinson's disease2016

    • Author(s)
      Sugama S, Kakinuma Y
    • Journal Title

      Neurosci Res

      Volume: 111 Pages: 48-55

    • DOI

      10.1016/j.neures.2016.04.008

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Chronic restraint stress triggers dopaminergic and noradrenergic neurodegeneration: Possible role of chronic stress in the onset of Parkinson's disease2016

    • Author(s)
      Sugama S, Sekiyama K, Kodama T, Takamatsu Y, Takenouchi T, Hashimoto M, Conti B, Kakinuma Y
    • Journal Title

      Brain Behav Immun

      Volume: 51 Pages: 39-46

    • DOI

      10.1016/j.bbi.2015.08.015

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Extracellular ATP induces unconventional release of glyceraldehyde-3-phosphate dehydrogenase from microglial cells2015

    • Author(s)
      Takenouchi T, Tsukimoto M, Iwamaru Y, Sugama S, Sekiyama K, Sato M, Kojima S, Hashimoto M, Kitani H
    • Journal Title

      Immunol Lett

      Volume: 167 Issue: 2 Pages: 116-124

    • DOI

      10.1016/j.imlet.2015.08.002

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Stress-induced microglial activation nullified in b1 and b2 adrenergic receptor double knockout mice2018

    • Author(s)
      Sugama S, Kakinuma Y
    • Organizer
      The 95th Annual Meeting of the Physiological Society Meeting
    • Related Report
      2017 Annual Research Report
  • [Presentation] Loss of dopaminergic neuronss occurs in the ventral tegmental area and hypothalamus of rats following chronic stress: Possible pathogenetic loci for depression involved in Parkinson's disease2017

    • Author(s)
      Sugama S, Kakinuma Y
    • Organizer
      日本生理学会
    • Place of Presentation
      浜松市
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] Chronic restraint stress triggers the dopaminergic and noradrenergic neurodegeneration-possible role of chronic stress in the onset of Parkinson's disease2016

    • Author(s)
      Sugama S, Kakinuma K
    • Organizer
      日本生理学会
    • Place of Presentation
      札幌市
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi