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Analysis of the mechanisims of protection of midbrain dopaminergic neurons by the innervation target with the usage of slice culture preparation

Research Project

Project/Area Number 12672110
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

KATSUKI Hiroshi  Kyoto University Graduate School of Pharmaceutical Sciences Department of Pharmacology Associate Professor, 薬学研究科, 助教授 (40240733)

Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsNitric oxide / Glutamate / Neuronal death / Reactive oxygen species / Dopamine neuron / Parkinson's disease
Research Abstract

This study was aimed to reveal factors contributing to the protection and the maintenance of functions of nigral dopaminergic neurons in the midbrain, using brain slice culture preparations. 1. Dopaminergic neurons in midbrain slice cultures acquired resistance to the cytotoxicity of NMDA and NO donors, when they were co-cultured with the striatal slices. NMDA-induced loss of dopaminergic neurons in single midbrain cultures was suppressed by an NO synthase inhibitor. The levels of ONOO production in dopaminergic neurons were higher in single midbrain cultures than in midbrain-striatum co-cultures. In addition, midbrain tissues co-cultured with the striatum exhibited an increased level of superoxide dismutase (SOD) activity as well as an increased level of Cu,Zn-SOD proteins, compared to midbrain tissues cultured alone. Therefore, interactions of the striatal tissue, an innervation target of the midbrain dopaminergic neurons, result in an increase in SOD within the midbrain, which may c … More ontribute to the increased resistance of dopaminergic neurons to excitotoxicity. 2. Cultivation of midbrain slices in the chronic presence of blockers of L-type voltage-dependent Ca^<2+> channels or voltage-dependent Na^+ channels was found to cause a dramatic decrease in the number of dopaminergic neurons. These effects were attenuated by concurrent treatments that caused elevation of intracellular levels of cyclic AMP, suggesting that spontaneous neuronal activity and resultant Ca^<2+> influx into neuronal cytoplasm contribute to the maintenance of dopaminergic neurons through the mechanisms involving cyclic AMP production. 3. A series of compounds with properties of s receptor ligands were found to afford remarkable protection of dopaminergic neurons against excitotoxic insults, by modulating the functions of NMDA receptors. These results revealed several aspects of endogenous protective systems for midbrain dopaminergic neurons, which may contribute to the establishment of novel strategies for prevention and treatment of Parkinson's disease. Less

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Kume, T. et al.: "p75-mediated neuroprotection by NGF against glutamate cytotoxicity in cortical cultures"Brain Res.. 852・2. 279-289 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shimazu, S. et al.: "σReceptor ligands attenuate N-methyl-D-aspartate cytotoxicity in dopaminergic neurons of mesencephalic slice cultures"Eur. J. Pharmacol.. 388・2. 139-146 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nishikawa, H. et al.: "Involvement of direct inhibition of NMDA receptors in the effects of σ-receptor ligands on glutamate neurotoxicity in vitro"Eur. J. Pharmacol.. 404・1/2. 41-48 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Katsuki, H. et al.: "Distinct signaling pathways involved in multiple effects of basic fibroblast growth factor on cultured rat hippocampal neurons"Brain Res.. 885.2. 240-250 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Katsuki, H. et al.: "Superoxide dismutase activity in organotypic midbrain-striatum co-cultures is associated with resistance of dopaminergic neurons to excitotoxicity"J. Neurochem.. 76・5. 1336-1345 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Katsuki, H. et al.: "Requirement of neural activity for the maintenance of dopaminergic neurons in rat midbrain slice cultures"Neurosci. Lett.. 300・3. 166-170 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shimazu, S. et al.: "(-)-1-(Benzofuran-2-yl)-2-propylaminopentane enhances locomotor activity in rats due to its ability to induce dopamine release"Eur. J. Pharmacol.. 421・3. 181-189 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ibi, M. et al.: "Protective effects of 1α,25-(OH)_2D_3 against the neurotoxicity of glutamate and reactive oxygen species in mesencephalic culture"Neuropharmacology. 40・6. 761-771 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 香月博志 他: "ドパミン受容体とParkinson病"別冊・医学のあゆみ7回膜貫通型受容体研究の新展開(佐藤公道、赤池昭紀編)医歯薬出版. 133-137 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 赤池昭紀: "グルタミン酸による延廷性神経細胞死に対するニコチンの保護作用"脳の科学. 22. 985-990 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kume, T. et al.: "p75-mediated neuroprotection by NGF against glutamate cytotoxicity in cortical cultures"Brain Res.. 852. 279-289 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shimazu, S. et al.: "σ Receptor ligands attenuate N-methyl-D-aspartate cytotoxicity in dopaminergic neurons of mesencephalic slice cultures"Eur. J. Pharmacol.. 388. 139-146 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nishikawa, H. et al.: "Involvement of direct inhibition of NMDA receptors in the effect of σ-receptor ligands on glutamate neurotoxicity in vitro"Eur. J. Pharmacol.. 404. 41-48 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Katsuki, H. et al.: "Distinct signaling pathways involved in multiple effects of basic fibroblast growth factor on cultured rat hippocampal neurons"Brain Res.. 885. 240-250 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Katsuki, H. et al.: "Superoxide dismutase activity in organotypic midbrain-striatum co-cultures is associated with resistance of dopaminergic neurons to excitotoxicity"J. Neurochem. 76. 1336-1345 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Katsuki, H. et al.: "Requirement of neural activity for the maintenance of dopaminergic neurons in rat midbrain slice cultures"Neurosci. Lett.. 300. 166-170 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shimazu, S. et al.: "(-) -1- (Benzofuran-2-yl)-2-propylaminopentane enhances locomotor activity in rats due to its ability to induce dopamine release"Eur. J. Pharmacol.. 421. 181-189 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ibi, M. et al.: "Protective effects of 1α,25-(OH)_2D_3 against the neurotoxicity of glutamate and reactive oxygen species in mesencephalic cultur"Neuropharmacology. 40. 761-771 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akaike, A. et al.: "Protective effects of nicotine against glutamate-induced delayed neuronal death. (in Japanese)"Nou-no-Kagaku. 40. 985-990 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Katsuki, H. et al.: "Dopamine receptors and Parkinson's disease"Igaku-no-Ayumi Supplement : New development of research on receptors with seven transmembrane domains (Eds. Satoh, M. and Akaike, A.) (in Japanese). 133-137 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Katsuki, H. et al.: "Superoxide dismutase activity in organotypic midbrain-striatum co-cultures is associated with resistance of dopaminergic neurons to excitotoxicity"J. Neurochem. 76・5. 1336-1345 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Katsuki, H. et al.: "Requirement of neural activity for the maintenance of dopaminergic neurons in rat midbrain slice cultures"Neurosci. Lett.. 300・3. 166-170 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ibi M.et al.: "Protective effects of 1α, 25-(OH)_2D_3 against neurotoxicity of glutamate and reactive oxygen species in mesencephalic culture"Neuropharmacology. 40・6. 761-771 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shimazu S. et al.: "(-)-1-(Benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP] enhances locomotor activities in rats due to its ability to induce dopamine release"Eur. J. Pharmacol. 421. 181-189 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 香月博志 他: "ドパミン受容体とParkinson病"別冊・医学のあゆみ 7回膜貫通型受容体研究の新展開 医歯薬出版. 133-137 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kume,T. et al.: "p75-mediated neuroprotection by NGF against glutamate cytotoxicity in cortical cultures."Brain Res.. 852(2). 279-289 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shimazu S. et al.: "σ Receptor ligands attenuate N-methyl-D-aspartate cytotoxicity in dopaminergic neurons of mesencephalic slice cultures."Eur.J.Pharmacol.. 388(2). 139-146 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nishikawa H. et al.: "Involvement of direct inhibition of NMDA receptors in the effects of σ-receptor ligands on glutamate neurotoxicity in vitro."Eur.J.Pharmacol.. 404(1-2). 41-48 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Katsuki H. et al.: "Distinct signaling pathways involved in multiple effects of basic fibroblast growth factor on cultured rat hippocampal neurons."Brain Res.. 885(2). 240-250 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 赤池昭紀 他: "グルタミン酸脳の科学 22巻 ニコチンの脳化学による遅延性神経細胞死に対するニコチンの保護作用"星和書店. 6 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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