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Study on the ischemia-induced neuronal injuries with special reference to alterations in the intracellular signaling cascades.

Research Project

Project/Area Number 09671432
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionKumamoto University

Principal Investigator

GOTO Satoshi  Kumamoto University, University Hospital, Lecturer, 医学部・附属病院, 講師 (50240916)

Co-Investigator(Kenkyū-buntansha) NISHI Toru  Kumamoto University, University Hospital, Assistant Professor, 医学部・附属病院, 助手 (00264309)
HAMADA Jun-ichiro  Kumamoto University, University Hospital, Assistant Professor, 医学部・附属病院, 助手 (40253752)
USHIO Yukitaka  Kumamoto University, Medical School, Professor, 医学部, 教授 (20028583)
永廣 信治  徳島大学, 医学部, 教授 (60145315)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsCerebral ischemia / N-methyl-D-aspartate / Striatum / GABA / Transplantation / Calcium signal / STEP / Tyrosine-phosphatase / NMDA receptor / GABA agonist / Second messenger / STEP / Tyrosine dephosphorylation / Neuronal development / 脳虚血 / 神経細胞死 / 細胞内情報伝達 / カルシウム
Research Abstract

In a series of our experiments, we have found that N-methyl-D--aspartate (NMDA) receptor coupled with intracellular calcium-signaling cascade is involved in the striatal ischemic injury and its remote effects on the target nuclei. Also, an intraventricular infusion of GABA receptor agonist promotes reformation of the striatonigral pathway by transplant derived from fetal striatal primordia in the striatal ischemic lesion. Furthermore, we have established an organotypic culture technique for the striatal tissue and then reproduced the NMDA-neurotoxicity on the striatal neurons in vitro which was not blocked by an activation of GABA_A receptor. In addition, overexpression of striatal enriched protein tyrosine phosphatase (STEP) was found to promote neuronal differentiation induced by a cAMP analogue in PC12 cells, suggesting that STEP may participate in neuronai modeling and/or plasticity. Therefore, we have a plan to elucidate whether a cell line changes its vulnerability to ischemic/anoxic insult by the STEP gene transfection.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Yamada,Goto et al.: "Continuous intraventricular drug infusion for the in vivo study of transneuronal degeneration in the striatonigral." Brain Research Protocols. 1. 371-377 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshikawa,Goto et al.: "Neurotoxicity evoked by N-methyl-D-aspartate(NMDA)in the oraganotypic static slice cultures of rat cerebrocortices." Acta Neuropathologica. 95. 592-596 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Goto et al.: "GABA receptor agonist promotes reformation of the striatonigral pathway by transplants derived from the fetal stria." Experimental Neurology. 147. 503-509 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Korematsu,Goto et al.: "Heterogeneity of cadherin-8 expression in the neonate rat striatum : comparison with striatal compartments." Experimental Neurology. 154. 531-536 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Okamura,Goto et al.: "Overexpression of striatal enriched phosphatase promotes neurite outgrowth induced by a cAMP analogue in PC12 cells." Molecular Brain Research. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 後藤恵 他3名: "カルシニューリンの構造と細胞機能調節" 蛋白質・核酸・酵素. 43. 1706-1714 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamada K., Goto S., Yoshikawa M., Okamura A., Ushio Y.: "Continuous intraventricular drua infusion for the in vivo study of transneuronal degeneration in the striatonigral system of the rat." Brain Research Protocols.1. 371-377 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshikawa M., Goto S., Okamura A., Hamasaki T., Ushio Y.: "Neurotoxicity evoked by N-methyl-D-aspartate (NMDA) in the organotypic static slice cultures of rat cerebrocortices." Acta Neuropathologica. 95. 592-596 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Goto S., Yamada K., Yoshikawa M., Okamura A., Ushio Y.: "GABA receptor agonist promotes reformation of the striatonigral pathway by transplants derived from fetal striatal primordia in the lesioned striatum." Experimental Neurology. 147. 503-509 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Korematsu K., Goto S., Okamura A., Ushio Y.: "Heterogeneity of cadherin-8 expression in the neonate rat striatum : Comparison with striatal compartments." Experimental Neurology. 154. 531-536 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Okamura A., Goto S., Nishi T., Hamasaki T., Ushio Y.: "Overexpression of striatal enriched phosphatase promotes neurite outgrowth induced by a cAMP analogue in PC12 cells." Molecular Brain Research. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Goto S., Yamamoto H., Hamasaki T., Miyamoto W.: "Calcineurin : Structure and regulation of the cellular functions." Proteins, Nucleic Acids and Enzymes. 43. 1706-1714 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshikawa,Goto et al.: "Neurotoxicity evoked by N-methyl-D-aspartate(NMDA)in the organotypic static slice cultures of rat cerebrocortices:..." Acta Neuropathlogica. 95. 593-596 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Okamura,Goto et al.: "Overexpression of striatal enriched phosphatase(STEP)promotes neurite outgrowth induced by a cAMP analogue in PC12 cells." Molecular Brain Research. in press.

    • Related Report
      1998 Annual Research Report
  • [Publications] Korematsu,Goto et al.: "Heterogeneity of cadherin-8 expression in the neonatal rat striatum:Comparison with the striatal compartments." Experimental Neurology. 154. 531-536 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Korematsu et al.: "Cadherin-8 expression in gray matter structures and nerve fibers in the neonatal and adult mouse brain." Neuroscience. 87. 303-315 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 後藤 恵: "カルシニューリンの構造と細胞機能調節" 蛋白質・核酸・酵素. 43. 1706-1714 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Inoue et al.: "Effetiveness os retrograde perfusion of the cerebral vein for attanuating neuronal injury after transinet ischemia in the rat." Neurol. Med. Chirur. (Tokyo). 37. 243-249 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamada, Goto et al.: "Intraventricular administration of GABAA receotor agonist muscimol attenuates the exo-focal change of the substantia nigra neurons" Neuropathol. (Tokyo). 17. 101-105 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Okamura, Goto et al.: "Postnatal ontogeny of striatal enriches protein tyrosine phosphatase (STEP) in rat striatum." Experimental Neurology. 145. 228-234 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Goto et al.: "GABA receptor abonist promotes reformation of the striatonigra pathway by transplants derived from fetal striatal primordia" Experimental Neurology. 147. 503-509 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamada, Goto et al.: "Continuous intraventricular drus infusion for the in vivo study of transneuronal degeneration in the striatonigral system of the rat." Brain Research Protocols. 1. 371-377 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshikawa, Goto, et al.: "Neurotoxicity evoked by N-methyl-D-aspartate (NMDA) in the organotypic static slice cultures of rat cerebrocortices." Acta Neuropathol.(in press).

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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