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Elucidation of the mechanism underlying the modulation of microglial function by antidepressants and/or BDNF

Research Project

Project/Area Number 20790847
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Psychiatric science
Research InstitutionKyushu University

Principal Investigator

MIZOGUCHI Yoshito  Kyushu University, 医学研究院, 特別教員 (60467892)

Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords脳由来神経栄養因子(BDNF) / ミクログリア / 気分障害 / うつ病 / カルシウム / 神経炎症 / 精神薬理 / BDNF / 抗うつ薬 / 薬理学 / 神経生理学
Research Abstract

Microglia are intrinsic immune cells that release factors, including proinflammatory cytokines, NO, and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca^<2+> concentration ([Ca^<2+>]i) is important for microglial functions, such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. In this study, we observed that BDNF induced a sustained increase in [Ca^<2+>]i through binding with the truncated tropomyosin-related kinase B receptor, resulting in activation of the PLC pathway and store-operated calcium entry in rodent microglial cells. RT-PCR and immunocytochemical techniques revealed that truncated tropomyosinrelated kinase B-T1receptors were highly expressed in rodent microglial cells. Sustained activation of store-operated calcium entry occurred after brief BDNF application and contributed to the maintenance of sustained [Ca^<2+>]i elevation. Pretreatment with BDNF significantly suppressed the release of NO from activated microglia. Additionally, pretreatment of BDNF suppressed the IFN-γ-induced increase in [Ca^<2+>]i, along with a rise in basal levels of [Ca^<2+>]i in rodent microglial cells. We show direct evidence that rodent microglial cells are able to respond to BDNF, which may be important for the regulation of inflammatory responses, and may also be involved in the pathophysiology and/or the treatment of neuropsychiatric disorders.

Report

(3 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • Research Products

    (14 results)

All 2009 2008 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (4 results)

  • [Journal Article] Brain-derived neurotrophic factor (BDNF) induces sustained elevation of intracellular Ca2+ in rodent microglia.2009

    • Author(s)
      Mizoguchi Y, Monji A, Kato T, Seki Y, Gotoh L, Horikawa H, Suzuki SO, Iwaki T, Yonaha M, Hashioka S, Kanba S
    • Journal Title

      J. Immunol. 183

      Pages: 7778-7786

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effect of yokukansan on the behavioral and psychological symptoms of dementia in elderly patients with Alzheimer's disease. Prog.2009

    • Author(s)
      Monji A, Takita M, Samejima T, Takaishi T, Hashimoto K, Matsunaga H, Oda M, Sumida Y, Mizoguchi Y, Kato T, Horikawa H, Kanba S
    • Journal Title

      Neuropsychopharamacol. Biol. Psychiatry 33

      Pages: 308-311

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Brain-derived neurotrophic factor (BDNF) induces sustained elevation of intracellular Ca^<2+> in rodent microglia2009

    • Author(s)
      Mizoguchi Y, et al.
    • Journal Title

      Journal of Immunology 183

      Pages: 7778-7786

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of yokukansan on the behavioral and psychological symptoms of dementia in elderly patients with Alzheimer's disease2009

    • Author(s)
      Monti A, et al.
    • Journal Title

      Prog.Neuropsychopharamacol. Biol.Psychiatry 33

      Pages: 308-311

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of yokukansan on the behavioral and psychological symptoms of dementia in elderly patients with Alzheimer's disease2009

    • Author(s)
      Monji A, et.al.
    • Journal Title

      Prog Neuropsychopharmacol Biol Psychiatry 33(2)

      Pages: 308-311

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibitory effects of aripiprazole on interferon-gamma-induced microglial activation via intracellular Ca2+ regulation in vitro.2008

    • Author(s)
      Kato T, Mizoguchi Y, Monji A, Horikawa H, Suzuki SO, Seki Y, Iwaki T, Hashioka S, Kanba S
    • Journal Title

      J. Neurochem. 106

      Pages: 815-25

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] The effect of atypical antipsychotics, perospirone, ziprasidone and quetiapine on microglial activation induced by interferon-γ.2008

    • Author(s)
      Bian Q, Kato T, Monji A, Hashioka S, Mizoguchi Y, Horikawa H, Kanba S
    • Journal Title

      Prog. Neuropsychopharamacol. Biol. Psychiatry 32

      Pages: 42-48

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibitory effects of aripiprazole on interferon-gamma-induced microglial activation via intracellular Caa^<2+> regulation in vitro2008

    • Author(s)
      Kato T, et.al.
    • Journal Title

      J Neurochem 106(2)

      Pages: 815-825

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of Cannabinoid 1 Receptor Protein and Messenger RNA in Monkey Dorsolateral Prefrontal Cortex.

    • Author(s)
      Eggan SM*, Mizoguchi Y*, Stoyak SR, Lewis DA.
    • Journal Title

      Cereb. Cortex (in the press)

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Development of Cannabinoid 1 Receptor Protein and Messenger RNA in Monkey Dorsolateral Prefrontal Cortex

    • Author(s)
      Eggan SM*, Mizoguchi Y*, et al. (* Equally contributed authors)
    • Journal Title

      Cerebral Cortex (In the press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Possible role of BDNF-induced microglial intracellular Ca2+ elevation in the pathophysiology of neuropsychiatric disoders.2009

    • Organizer
      Society for Neuroscience 2009 in Chicago
    • Place of Presentation
      McCormick Place
    • Year and Date
      2009-10-21
    • Related Report
      2009 Final Research Report
  • [Presentation] Possible role of BDNF-induced microglial intracellular Ca2+ elevation in the pathophysiology of neuropsychiatric disoders2009

    • Author(s)
      Mizoguchi, et al.
    • Organizer
      Society for Neuroscience 2009 in Chicago
    • Place of Presentation
      McCormick Place
    • Year and Date
      2009-10-21
    • Related Report
      2009 Annual Research Report
  • [Presentation] Possible role of BDNF-induced microglial intracellular Ca2+ elevation in the pathophysiology of neuropsychiatric disoders.2008

    • Organizer
      XIV World Congress of Psychiatry 2008
    • Place of Presentation
      Prague Congress Centre
    • Year and Date
      2008-09-21
    • Related Report
      2009 Final Research Report
  • [Presentation] Possible Roles of BDNF-induced Microglial Intracellular Ca^<2+> Elevation in the Pathophysiology of Psychiatric Disorders2008

    • Author(s)
      Mizoguchi Y, et.al.
    • Organizer
      XIV World Congress of Psychiatry
    • Place of Presentation
      Prague Congress Centre
    • Year and Date
      2008-09-21
    • Related Report
      2008 Annual Research Report

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

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