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2011 Fiscal Year Final Research Report

Investigation of stress-induced microglial activation

Research Project

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Project/Area Number 20500359
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurophysiology and muscle physiology
Research InstitutionNippon Medical School

Principal Investigator

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

Project Period (FY) 2008 – 2011
Keywordsグリア / 神経免疫学
Research Abstract

In the present study, we investigated microglial activation mechanism. With using microglia cell-line(MG6) as well as primary microglial cells, we employed RT-PCR, Western Blotting. Both in cell line and primary microglia, the expression of adrenergic receptor(AR) beta1 and beta2, but not beta3, was detected. Then, we administered an agonist for AR, isoproterenol. The result showed that isoproterenol did not affect the induction of interleukin-6.In addition, we studied an effect of adrenal steroid on microglial activation. It was shown that the expression of proinflammatory cytokines, such as interleukin-1, interleukin-6, was significantly inhibited by the adrenal steroid, dexamethazone. Furthermore, we studied the involvement of AR in microglial activation in vivo. In double knockout mouse that specifically lacks AR beta1 and beta2, microglial activation was not induced by exposure of restraint stress. The result was in contrast to that of wild type mouse which demonstrated significant stress-induced microglial activation in the brain. Thus, it was suggested that, in acute stress, microglial activation may be modulated through sympathetic nervous system, AR beta 1 and beta2.It was also suggested that adrenal glucocorticoids may play inhibitory roles in microglial activation.

  • Research Products

    (15 results)

All 2012 2011 2010 2009 2008

All Journal Article (12 results) Presentation (3 results)

  • [Journal Article] Ibuprofen ameliorates protein aggregation and astrocytic gliosis, but not cognitive dysfunction, in a transgenic mouse expressing dementia with Lewy bodies-linked P123H b-synuclein2012

    • Author(s)
      S ekiyama K, Fujita M, Sekigawa A, Takamatsu Y, Waragai M, Takenouchi T, Sugama S, Hashimoto M
    • Journal Title

      Neurosci Lett

      Volume: 515(1) Pages: 97-101

    • DOI

      Doi:10.1016/j.neulet.2012.03.037

  • [Journal Article] Theaflavins stimulate autophagic degradation of a-synuclein in neuronal cells2012

    • Author(s)
      T, Waragai M, Wei J, Sekigawa A, Takamatsu Y, Sugama S, Kitani H, Hashimoto M
    • Journal Title

      Open Journal of Neuroscience

      Volume: 2-1

    • URL

      http://www.rossscience.org/ojns/articles/2075-9088-2-1.pdf

  • [Journal Article] The activation of P2X7 receptor induces cathepsin D-dependent production of a 20-kDa form of IL-1b under acidic extracellular pH in LPS-primed microglial cells2011

    • Author(s)
      T akenouchi T, Iwamaru Y, Sugama S, Tsukimoto M, Fujita M, Sekigawa A, Sekiyama K, Sato M, Kojima S, Conti B, Hashimoto M, Kitani H
    • Journal Title

      J. Neurochem

      Volume: 117 Pages: 712-723

    • DOI

      doi:10.1111/j.1471-4159.2011.07240.x

  • [Journal Article] Immunological responses of astroglia in the rat brain under acute stress : interleukin-1 beta co-localized in astroglia2011

    • Author(s)
      Sugama S, Takenouchi T, Sekiyama K, Kitani H, Hashimoto M
    • Journal Title

      Neuroscience

      Volume: 192 Pages: 429-437

    • DOI

      Doi:10.1016/j.neuroscience.2011.06.051

  • [Journal Article] Cold stress induced morphological microglial activation and increased IL-1βexpression in astroglial cells in rat brain2011

    • Author(s)
      Sugama S, Takenouchi T, Fujita M, Kitani H, Hashimoto M
    • Journal Title

      J. Neuroimmunol

      Volume: 233 Pages: 29-36

    • DOI

      Doi:10.1016/j.jneuroim.2010.11.002

  • [Journal Article] Aβ-synuclein mutation linked to dementia produces neurodegeneration when expressed in mouse brain2010

    • Author(s)
      Fujita M, Sugama S, Sekiyama K, Sekigawa A, Tsukui T, Nakai M, Waragai M, Takenouchi T, Takamatsu Y, Wei J, Rochenstein E, Laspada AR, Masliah E, Inoue S, Hashimoto M
    • Journal Title

      Nat Commun

      Volume: 1 Pages: 110

    • DOI

      Doi:10.1038/ncomms1101

  • [Journal Article] Microglial activation is inhibited by corticosterone in dopaminergic neurodegeneration2009

    • Author(s)
      Sugama S, Takenouchi T, Kitani H, Fujita M, Hashimoto M
    • Journal Title

      J. Neuroimmunol

      Volume: 208(1-2) Pages: 104-114

    • DOI

      Doi:10.1016/j.jneuroim.2009.01.016

  • [Journal Article] Protective role of endogeneous gangliosides for lysosomal pathology in a cellular model of synuclenopathies2009

    • Author(s)
      Wei J, Fujita M, Nakai M, Waragai M, Sekigawa A, Sugama S, Takenouchi T, Masliah E, Hashimoto M
    • Journal Title

      Am. J. Pathol

      Volume: 174(5) Pages: 1891-909

    • DOI

      doi:10.2353/ajpath.2009.080680

  • [Journal Article] The role of the P2X7 receptor signaling pathway for the release of autolysosomes in microglial cells2009

    • Author(s)
      T akenouchi T, Fujita M, Sugama S, Kitani H, Hashimoto M
    • Journal Title

      Autophagy

      Volume: 5(5) Pages: 723-724

    • DOI

      Doi:10.4161/auto.5.5.8478

  • [Journal Article] Stress-induced microglial activation may facilitate the progression of neurodegenerative disorders2009

    • Author(s)
      Sugama S
    • Journal Title

      Medical Hypotheses

      Volume: 73 Pages: 1031-1034

    • DOI

      Doi:10.1016/j.mehy.2009.02.047

  • [Journal Article] Differential microglial activation between acute stress and lipopolysaccharide administration2009

    • Author(s)
      Sugama S, Takenouchi T, Conti B, Hashimoto M
    • Journal Title

      J. Neuroimmunol

      Volume: 207(1-2) Pages: 24-31

    • DOI

      Doi:10.1016/j.jneuroim.2008.11.007

  • [Journal Article] Lysoshospolipids and ATP mutually suppress maturation and release of IL-1beta in mouse microglial cells using a Rho-dependent pathway2008

    • Author(s)
      T akenouchi T, Iwamaru Y, Sugama S, Sato M, Hashimoto M, Kitani H
    • Journal Title

      J. Immunol

      Volume: 180(12) Pages: 7827-39

    • URL

      http://www.jimmunol.org/content/180/12/7827

  • [Presentation] Cold stress induced morphological microglial activation and increased IL-1βexpression in astroglial cells in rat brain2011

    • Author(s)
      Sugama S
    • Organizer
      第88回日本生理学会
    • Place of Presentation
      横浜
    • Year and Date
      2011-03-28
  • [Presentation] Astroglial response may differ from that of microglial cells in response to acute stress2010

    • Author(s)
      Sugama S
    • Organizer
      第87回日本生理学会
    • Place of Presentation
      盛岡
    • Year and Date
      2010-05-19
  • [Presentation] Differential microglial activation between acute stress and lipopolysaccharide treatment2009

    • Author(s)
      Sugama S
    • Organizer
      第86回日本生理学会(第36回国際生理学会)
    • Year and Date
      2009-07-28

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Published: 2013-07-31  

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