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THE STUDY OF THE THERAPEUTIC MECHANISMS OF ANTIDEPRESSANT ON NEURONAL REMODELING

Research Project

Project/Area Number 14570943
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionSHOWA UNIVERSITY

Principal Investigator

YAMADA Mitsuhiko  SHOWA UNIVERSITY SCH. MEDICINE, DEPT PSYCHIAT, ASSISTANT PROFESSOR, 医学部, 講師 (60240040)

Co-Investigator(Kenkyū-buntansha) MOMOSE Kazutaka  SHOWA UNIVERSITY SCH. PHARMACEUTICAL SCI, DEPT PHARMACOL, PROFESSOR, 薬学部, 教授 (80004597)
KAMIJIMA Kunotoshi  SHOWA UNIVERSITY SCH. MEDICINE, DEPT PSYCHIAT, PROFESSOR, 医学部, 教授 (80051613)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsantidepressant / neuroplasticity / rat / brain / gene / molecular biology / differential cloning / microarray / Differential Cloning
Research Abstract

We have previously identified 200 cDNA fragments as antidepressant related genes (ADRG) from rat frontal cortex and hypothalamus using differential cloning technique. In the present study, we continued this screening in rat hippocampus and identified total of 707 cDNA and developed the ADRG microarray. More recently, we used ADRG microarray to search for s**e genes commonly induced after chronic antidepressant treatment and repeated ECT. ECT is another therapy for depressive patients that is widely used, particularly in the treatment of patients who are resistant to antidepressant medications. Interestingly, we found some genes related to neurite outgrowth, were commonly induced or decreased after chronic antidepressant treatment and repeated ECT. Thus, the unknown candidate ADRG genes may be thought that belong to the function related to the neurite outgrowth. ADRG#102 and ADRG#123 were subcloned to GFP expression vector and transfected to NGF-induced differentiated PC12 cels. Measurement of the morphological changes demonstrated that the mean length of the longest neurite in each cell and the total length of neurites per cell was significantly shorter in the transfectants, respectively. In addition, the mean neurite number per cell was also significantly smaller in the transfectants. One of the long-term therapeutic action of antidepressant may be related to the changes of both functional and structural neuroplasticity.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Yamada et al.: "Differential expression of VAMP2/synaptobrevin-2 after antidepressant and electroconvulsive treatment in rat frontal cortex"Pharmacogenomics J.. 2. 277-382 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishioka et al.: "Induction of kf-1 after repeated electroconvulsive treatment and chronic antidepressant treatment in rat frontal cortex and hippocampus."J.Neural.Trans.. 110. 277-285 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada et al.: "Antidepressant-elicited changes in gene expression -Remodeling of neuronal circuits as a new hypothesis for drug efficacy."Prog Neuropsychopharmacol Biol Psychiatry. in press. (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada et al.: "Antidepressant research in the era of functional genomics - Farewell to the monoamine hypothesis-"Biogenic Amines. in press. (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada, et al.: "Differential expression of VAMP2/synaptobrevin-2 after antidepressant and electroconvulsive treatment in rat frontal cortex."Pharmacogenomics J. 2. 377-382 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishioka et al.: "Induction of kf-1 after repeated electroconvulsive treatment and chronic antidepressant treatment in rat frontal cortex and hippocampus."J.Neural.Trans.. 110. 277-285 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada et al.: "Antidepressant-elicited changes in gene expression -Remodeling of neuronal circuits as a new hypothesis for drug efficacy."Prog Neuropsychopharmacol Biol Psychiatry. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada et al.: "Antidepressant research in the era of functional genomics-Farewell to the monoamine hypothesis-"

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishioka et al.: "Induction of kf-1 after repeated electroconvulsive treatment and chronic antidepressant treatment in rat frontal cortex and hippocampus"J.Neural.Trans.. 110. 277-285 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamada et al.: "Antidepressant-elicited changes in gene expression -Remodeling of neuronal circuits as a new hypothesis for drug efficacy"Prog Neuropsychopharmacol Biol Psychiatry. in press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamada et al.: "Antidepressant research in the era of functional genomics - Farewell to the monoamine hypothesis -"Biogenic Amines. in press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamada, M.et al.: "Differential expression of VAMP2/synaptobrevin-2 after antidepressant and electroconvulsive treatment in rat frontal cortex"Pharmacogenomics J.. 2. 377-382 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nishioka.G.et al.: "Induction of kf-1 after repeated electroconvulsive treatment and chronic antidepressant treatment in rat frontal cortex and hippocampus"J. Neural. Trans.. (in press). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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