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Phosphodiesterase 4 inhibition enhances the dopamine D1 receptor/PKA signaling cascade in frontal cortex.

Research Project

Project/Area Number 22890228
Research Category

Grant-in-Aid for Research Activity Start-up

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

Principal Investigator

KUROIWA Mahomi  久留米大学, 医学部, 助教 (20585690)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,068,000 (Direct Cost: ¥2,360,000、Indirect Cost: ¥708,000)
Fiscal Year 2011: ¥1,469,000 (Direct Cost: ¥1,130,000、Indirect Cost: ¥339,000)
Fiscal Year 2010: ¥1,599,000 (Direct Cost: ¥1,230,000、Indirect Cost: ¥369,000)
Keywordsホスホジエステラーゼ / 統合失調症 / 大脳皮質 / DARPP-32 / ドーパミン / 認知機能障害
Research Abstract

Alteration of dopamine neurotransmission in the prefrontal cortex, especially hypofunction of dopamine D1 receptors, contributes to psychotic symptoms and cognitive deficit in schizophrenia. D1 receptors signal through the cAMP/PKA second messenger cascade, which is modulated by phosphodiesterase(PDE) enzymes that hydrolyze and inactivate cyclic nucleotides. Though several PDEs are expressed in cortical neurons, the PDE4 enzyme family(PDE4A-D) has been implicated in the control of cognitive function. We revealed that PDE4, which is expressed in D1 receptor-positive cortical pyramidal neurons in layer VI, modulates the level of D1 receptor signaling in the frontal cortex, likely influencing cognitive function. These biochemical and behavioral actions of PDE4 inhibitors may contribute to the hypothesized antipsychotic actions of this class of compounds.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (11 results)

All 2012 2011 2010

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (7 results)

  • [Journal Article] Phosphodiesterase 4 inhibition enhances the dopamine D1receptor/PKA/D ARPP-32 signaling cascade in frontal cortex2012

    • Author(s)
      Kuroiwa, M., et al
    • Journal Title

      Psychopharmacology

      Volume: 219 Issue: 4 Pages: 1065-1079

    • DOI

      10.1007/s00213-011-2436-8

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mechanisms for the modulation of dopamine d(1) receptor signaling in striatal neurons2011

    • Author(s)
      Nishi A, Kuroiwa M, Shuto T.
    • Journal Title

      Frontiers in neuroanatomy

      Volume: vol.5 No.43

    • DOI

      10.3389/fnana.2011.00043

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of adrenoceptors in the regulation of dopamine/DARPP-32 signaling in neostriatal neurons2010

    • Author(s)
      Hara M, Fukui R, Hieda E, Kuroiwa M, Bateup HS, Kano T, Greengard P, Nishi A.
    • Journal Title

      Journal of neurochemistry

      Volume: vol.113 No.4 Issue: 4 Pages: 1046-59

    • DOI

      10.1111/j.1471-4159.2010.06668.x

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of adrenoceptors in the regulation of dopamine/DARPP-32 signaling in neostriatal neurons.2010

    • Author(s)
      Masato Hara
    • Journal Title

      Journal of neurochemistry

      Volume: 113 Pages: 1046-1059

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] コカインにより活性化される線条体ドーパミンD1受容体シグナルに対するレスベラトロールの影響2012

    • Author(s)
      首藤隆秀
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      2012-03-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Effect of fluoxetine in dopamine D1 receptor signaling in the hippocampal dentate gyrus2011

    • Author(s)
      黒岩真帆美
    • Organizer
      第41回神経精神薬理学会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Year and Date
      2011-10-28
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] ムスカリン受容体による線条体ドーパミン情報伝達系の調節2011

    • Author(s)
      黒岩真帆美
    • Organizer
      第84回日本薬理学会年会
    • Place of Presentation
      誌上開催
    • Year and Date
      2011-03-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] sirtuinを活性化するresveratrolのコカイン逆耐性現象に対する影響2011

    • Author(s)
      古賀夕貴
    • Organizer
      第84回日本薬理学会年会
    • Place of Presentation
      誌上開催
    • Year and Date
      2011-03-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] Regulation of DARPP-32 phosphorylation by muscarinic receptors via presynaptic and postsynaptic mechanisms in the striatum2010

    • Author(s)
      黒岩真帆美
    • Organizer
      第63回日本薬理学会西南部会
    • Place of Presentation
      鹿児島県民交流センター(鹿児島県)
    • Year and Date
      2010-11-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] ドーパミン細胞質・核内DARPP-32シグナルのグルタミン酸による制御2010

    • Author(s)
      西昭徳
    • Organizer
      第63回日本薬理学会西南部会
    • Place of Presentation
      鹿児島県民交流センター(鹿児島県)
    • Year and Date
      2010-11-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] 大脳皮質ドーパミンD1シグナルを制御するホスホジエステラーゼ4に関する研究2010

    • Author(s)
      黒岩真帆美
    • Organizer
      第40回日本神経精神薬理学会年会
    • Place of Presentation
      仙台国際センター(宮城県)
    • Year and Date
      2010-09-17
    • Related Report
      2011 Final Research Report 2010 Annual Research Report

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Published: 2010-08-27   Modified: 2016-04-21  

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