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Investigation of stress-induced microglial activation

Research Project

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

Project Period (FY) 2008 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsグリア / 神経免疫学 / 拘束ストレス / ミクログリア / ノルアドレナリン受容体 / 副腎皮質ステロイド / LPS / イソプロテレノロール / ダブルノックアウトマウス / RT-PCR / ストレス / アストロサイト / 寒冷刺激 / インターロイキン1β / 海馬 / 視床下部 / 交感神経系 / アストログリア / 中枢神経 / サイトカイン / インターロイキン1 / 感染 / 中心灰白質 / Fos蛋白 / グルタミン酸 / ノルアドレナリン
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.

Report

(6 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report   Self-evaluation Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (54 results)

All 2012 2011 2010 2009 2008 Other

All Journal Article (46 results) (of which Peer Reviewed: 25 results) Presentation (8 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) Issue: 1 Pages: 97-101

    • DOI

      10.1016/j.neulet.2012.03.037

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [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

    • Related Report
      2011 Final Research Report
  • [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

      10.1111/j.1471-4159.2011.07240.x

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [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

      10.1016/j.neuroscience.2011.06.051

    • Related Report
      2011 Final Research Report
  • [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 Issue: 1-2 Pages: 29-36

    • DOI

      10.1016/j.jneuroim.2010.11.002

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [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)
      Takenouchi 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

      Journal of Neurchemistry

      Volume: 117 Pages: 712-723

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cold stress induced morphological microglial activation and increased IL-1b expression in astroglial cells in rat brain2011

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

      Journal of Neuroimmunology

      Volume: 233 Pages: 29-36

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunological responses of astroglia in the rat brain under acute stress : interletikin-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

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [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 Issue: 1 Pages: 110-110

    • DOI

      10.1038/ncomms1101

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] P2X7 receptor signaling pathway as a therapeutic target for neurodegenerative diseases.2010

    • Author(s)
      Takenouchi T, Sekiyama K, Sekigawa A, Fujita M, Waragai M, Sugama S, Iwamaru Y, Kitani H, Hashimot M.
    • Journal Title

      Arch Immunol Ther Exp (Warsz). 58

      Pages: 91-96

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Ab-synuclein mtation linked to dementia produces neurodegeneration when expressed in mouse brain.2010

    • Author(s)
      Fujita M, Sugama S, Sekiyama K, Sekigawa A, et al.
    • Journal Title

      Nature Communications

      Volume: 1 Pages: 110-110

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] P2X7 receptors signaling pathway as a therapeutic target for neurodege nerative diseases.2010

    • Author(s)
      Takenouchi T, Sekiyama K, Sekigawa A, Fujita M, Waragai M, Sugama S, et al.
    • Journal Title

      Arch Immunol Ther Exp (Warsz)

      Volume: 58 Pages: 91-91

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-18 in the CNS2010

    • Author(s)
      Alboni S, Cervia D, Sugama S, Conti B
    • Journal Title

      J Neuroinflammation 7

      Pages: 9-9

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] P2X7 receptor signaling pathway as a therapeutic target for neurodegenerative diseases2010

    • Author(s)
      Takenouchi T, Sekiyama K, Sekigawa A, Fujita M, Waragai M, Sugama S, Iwamaru Y, Kitani H, Hashimot M
    • Journal Title

      Arch Immunol Ther Exp (Warsz) 58

      Pages: 91-96

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [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) Issue: 1-2 Pages: 104-114

    • DOI

      10.1016/j.jneuroim.2009.01.016

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [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) Issue: 5 Pages: 1891-909

    • DOI

      10.2353/ajpath.2009.080680

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [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) Issue: 5 Pages: 723-724

    • DOI

      10.4161/auto.5.5.8478

    • Related Report
      2011 Final Research Report
  • [Journal Article] Stress-induced microglial activation may facilitate the progression of neurodegenerative disorders2009

    • Author(s)
      Sugama S
    • Journal Title

      Medical Hypotheses

      Volume: 73 Issue: 6 Pages: 1031-1034

    • DOI

      10.1016/j.mehy.2009.02.047

    • Related Report
      2011 Final Research Report
  • [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) Issue: 1-2 Pages: 24-31

    • DOI

      10.1016/j.jneuroim.2008.11.007

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential microglial activation between acute stress and lipopolysaccharide treatment.2009

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

      J.Neuroimmunol 207

      Pages: 24-31

    • Related Report
      2010 Self-evaluation Report
  • [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. 208

      Pages: 104-114

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] The activation of P2X7 receptor impairs lysosomal functions and stimulates the release of autophagolysosomes in microglial cells2009

    • Author(s)
      Takenouchi T, Nakai M, Iwamaru Y, Sugama S, Tsukimoto M, Fujita M, Wei J, Sekigawa A, Sato M, Kojima S, Kitani H, Hashimoto M.
    • Journal Title

      J.Immunol. 182

      Pages: 2051-2062

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Lysophospholipids and ATP mutually suppress maturation and release of IL-1 beta in mouse microglial cells using Rho-dependent pathway.2009

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

      J.Immunol. 180

      Pages: 7827-7839

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] The role of P2X7 receptor impairs lysosomal functions and stimulates the release of autophagolysosomes in microglial cells2009

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

      Autophagy 5

      Pages: 723-724

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Protective role of endogenous gangliosides for lysosomal pathology in a cellular model of synucleinopathies2009

    • 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. 174

      Pages: 1891-1909

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Mapping of the full length and the truncated interleukin-18 receptor alpha in the mouse brain.2009

    • Author(s)
      Alboni S, Cervia D, Ross B, Montanari C, Gonzalex AS, Sanchez-Alavez M, Marcondes MC, De Vries D, Sugama S, Brunello N, Blom J, Tascedda F, Conti B.
    • Journal Title

      J.Neuroimmunol. 214

      Pages: 43-54

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Neurotoxic conversion of beta-synuclein : a novel approach to generate a transgenic mouse model of synucleinopathies?2009

    • Author(s)
      Fujita M, Sekigawa A, Sekiyama K, Sugama S, Hashimoto M.
    • Journal Title

      J Neurol. 256

      Pages: 286-292

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Possible roles of microglial cells for neurotoxicity in clinical neurodegenerative diseases and experimental animal models2009

    • Author(s)
      Sugama S, Takenouchi T, Cho BP, Joh TH, Hashimoto M, Kitani H.
    • Journal Title

      Inflamma Allergy Drug Targets 8

      Pages: 277-284

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Interleukin-18 in the CNS2009

    • Author(s)
      Alboni S, Cervia D, Sugama S, Conti B
    • Journal Title

      J Neuroinflammation 29

      Pages: 7-9

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] The role of the P2X7 receptor signaling pathway for the release of autolysosomes in microglial cells2009

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

      Autophagy 5

      Pages: 723-724

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protective role of endogenous gangliosides for lysosomal pathology in a cellular model of synucleinopathies2009

    • 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 174

      Pages: 1891-1909

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stress-induced microglial activation may facilitate the progression of neurodegenerative disorders2009

    • Author(s)
      Sugama S
    • Journal Title

      Med Hypotheses 73

      Pages: 1031-1034

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Mapping of the full length and the truncated interleukin-18 receptor alpha in the mouse brain2009

    • Author(s)
      Alboni S, Cervia D, Ross B, Montanari C, Gonzalex AS, Sanchez-Alavez M, Marcondes MC, De Vries D, Sugama S, Brunello N, Blom J, Tascedda F, Conti B
    • Journal Title

      J Neuroimmunol 214

      Pages: 43-54

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulation of the ATP-induced release and processing of IL-1beta in microglial cells2009

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

      Crit Rev Immunol 29

      Pages: 335-345

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neurotoxic conversion of beta-synuclein : a novel approach to generate a transgenic mouse model of synucleinopathies?2009

    • Author(s)
      Fujita M, Sekigawa A, Sekiyama K, Sugama S, Hashimoto M
    • Journal Title

      J Neurol 256

      Pages: 286-292

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible roles of microglial cells for neurotoxicity in clinical neurode generative diseases and experimental animal models2009

    • Author(s)
      Sugama S, Takenouchi T, Cho BP, Joh TH, Hashimoto M, Kitani H
    • Journal Title

      Inflamma Allergy Drug Targets 8

      Pages: 277-284

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential microglial activation between acute stress and lipopolysaccharide treatment2009

    • Author(s)
      Sugama S, Takenouchi T, Fujita M, Conti B, et al.
    • Journal Title

      Journal of Neuroimmunology 207

      Pages: 24-31

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Microglial activation is inhibited by corticosterone in dopaminergic neurodegeneration2009

    • Author(s)
      Sugama S, Takenouchi T, Kitani H, et al.
    • Journal Title

      Journal of Neuroimmunology 208

      Pages: 104-114

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The activation of P2X7 receptor impair lysosomal functions and stimulatesthe release of autophagolysosomes in microglial cells.2009

    • Author(s)
      Takenouchi T, Nakai M, Iwamaru Y, Sugama, et al.
    • Journal Title

      Journal of Immunology 182

      Pages: 205-262

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [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

    • Related Report
      2011 Final Research Report
  • [Journal Article] Interleukin-18 and stress.2008

    • Author(s)
      Sugama S, Conti B.
    • Journal Title

      Brain res Rev. 58

      Pages: 85-95

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Lysophospholipids and ATP mutually suppress maturation and release of IL-1 beta in mouse microglial cells using a Rho-dependent pathway2008

    • Author(s)
      Takenouchi T, Iwamaru Y, Sugama S, et al.
    • Journal Title

      Journal of Immunology 180

      Pages: 7827-39

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-18 and stress2008

    • Author(s)
      Sugama S, Conti B
    • Journal Title

      Brain Res Rev 58

      Pages: 85-95

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stress-induced microglial activation may facilitate the progression of neurodegenerative disorders.

    • Author(s)
      Sugama S
    • Journal Title

      Medical Hypotheses 73

      Pages: 1031-1034

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Modulation of the ATP-induced release and processing of IL-1beta in microglial cells.

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

      Crit Rev Immunol 29

      Pages: 335-345

    • Related Report
      2010 Self-evaluation Report
  • [Journal Article] Ab-synuclein mtation linked to dementia produces neurodegeneration when expressed in mouse brain.

    • Author(s)
      Fujita M, Sugama S, Sekiyama K, Sekigawa A, et al..
    • Journal Title

      Nature Communications 1

      Pages: 110-110

    • Related Report
      2010 Self-evaluation Report
  • [Presentation] Immunological responses of astroglia in the rat brain under acute stress2012

    • Author(s)
      Sugama S
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      松本市
    • Year and Date
      2012-03-29
    • Related Report
      2011 Annual Research Report
  • [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
    • Related Report
      2011 Final Research Report
  • [Presentation] Cold stress induced morphological microglial activation and increased IL-1b expression in astroglial cells in rat brain.2011

    • Author(s)
      Sugama S
    • Organizer
      第88回日本生理学会大会
    • Related Report
      2010 Self-evaluation Report
  • [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
    • Related Report
      2011 Final Research Report
  • [Presentation] Astroglial response may differ from that of microglial cells in response to acute stress.2010

    • Author(s)
      Sugama S
    • Organizer
      第87回日本生理学会大会
    • Place of Presentation
      盛岡市
    • Year and Date
      2010-05-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] Astroglial response may differ from that of microglial cells in response to acute stress2010

    • Author(s)
      Sugama S
    • Organizer
      第87回日本生理学会大会
    • Related Report
      2010 Self-evaluation Report
  • [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
    • Related Report
      2011 Final Research Report
  • [Presentation] Differential microglial activation between acute stress and lipopolysaccharide treatment2009

    • Author(s)
      Sugama S
    • Organizer
      第36回国際生理学会大会(第86回日本生理学会大会)
    • Related Report
      2010 Self-evaluation Report 2009 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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