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2002 Fiscal Year Final Research Report Summary

Role of glia in ischemia-induced and MPTP-induced neuronal deaths

Research Project

Project/Area Number 13670627
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionTohoku University

Principal Investigator

KATO Hiroyuki  Tohoku University, Graduate School of Medicine, Associate professor, 大学院・医学系研究科, 助教授 (60224531)

Co-Investigator(Kenkyū-buntansha) ITOYAMA Yasuto  Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (30136428)
TAKAHASHI Akira  Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40301048)
ARAKI Tsutomu  Tohoku University, Graduate School of Pharmaceutical Science, Associate professor, 大学院・薬学研究科, 助教授 (80323038)
Project Period (FY) 2001 – 2002
KeywordsCelebral ischemia / Celecral infarction / Neuronal death / Parkinson's disease / MPTP / Dopamine / Microglia / Astroglia
Research Abstract

The purpose of this study was to clarify the role of glial cells in the development of ischemia-induced and MPTP-induced neuronal deaths. (1) Cerebral ischemia (10 min) was induced by the 2-vessel occlusion method in rats, which were sacrificed after 1 day, 2 days, and 7 days for double label immunohistochemistry. Expression of cell cycle proteins occurred prior to CAI neuronal death, and played a role in microglial proliferation. Proliferating cell nuclear antigen (PCNA) was expressed in 83% of microglial cells in CAI after 2 days. The number of microglial cells increased by 7.6-fold after 7 days CAI neurons were depleted. Cell cycle proteins, cyclin D1 and cdk4, were induced in microglia in a similar fashion. PCNA was expressed only in 6% of astrocytes in CAI after 7 days, when astroglial proliferation was only 1.8-fold. We observed no cell cycle protein expression in neurons. (2) MPTP (20 mg/kg) was injected i.p. 4 times 2 hr apart to mice. The content of dopamine in striatum was reduced to 16% of control after 1 day, and was remained as low as 22% after 14 days. ONO-2506, an astroglial function modulating agent, administered immediately, 6 hr, 24 hrs, 48 hrs, and 72 hrs after MPTP injection prevented the dopamine depletion, and led to better performance in behavioral tests. Astrocytes in striatum were activated markedly after 7 days, and ONO-2506 treatment resulted in earlier activation of asrtrocytes. The findings suggest that astrocytes may be a target for neuroprotection in MPTP induced neuronal death, and possibly in Parkinson's disease.

  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Muramatsu Y,.., Kato H, et al.: "Therapeutic effect of neuronal nitric oxide synthase inhibitor (7-nitroindazole) against MPTP neurotoxicity in mice"Metab Brain Dis. 17. 169-182 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kurosaki R,.., Kato H, et al.: "Role of nitric oxide synthase against MPTP neurotoxicity in mice"Neurol Res. 24. 655-662 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Lee T-H, Kato H, et al.: "Expression disparity of brain-derived neurotrophic factor immunoreactivity and mRNA in ischemic hippocampal neurons"NeuroReport. 13. 2271-2275 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kato H, et al.: "Protection of dopaminergic neurons with a novel astrocyte modulating agent (R)-(-)-2-propyloctanoic acid (ONO-2506) in an MPTP-mouse model of Parkinson's disease"J Neurol Sci. (In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kato H, et al.: "Cell cycle protein expression in proliferating microglia and astrocytes following transient global cerebral ischemia in the rat"Brain Res Bull. (In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 加藤宏之, 荒木勉, 他: "パーキンソン病モデルマウスにおけるNOS阻害薬とMAO阻害薬の脳保護作用"Prog Med. 22. 206-211 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 黒崎瑠美子, 加藤宏之, 他: "実験的パーキンソン病モデルマウスにおける基礎的検討"Prog Med. 22. 2894-2900 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 加藤宏之: "脳機能の開明.生命科学の主潮流"イムノフィリンFK506 binding protein-12の脳内分布と脳虚血後の変化""ガイヤ出版会. 267-273 (2002)

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      「研究成果報告書概要(和文)」より
  • [Publications] Kato H, Takahashi A, Itoyama Y: "Maturation Phenomenon in Cerebral Ischemia V "Microglial proliferation and cell cycle protein upregulation in the rat hippocampus following forebrain ischemia""Springer-Verlag(In press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Muramatsu Y, Kurosaki R, Mikami T, Michimata M, Matsubara M, Imai Y, Kato H, Itoyama Y, Araki T: "Therapeutic effect of neuronal nitric oxide synthase inhibitor (7-nitroindazole) against MPTP neurotoxicity in mice"Metab Brain Dis. 17. 169-182 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurosaki R, Muramatsu Y, Michimata M, Matsubara M, Kato H, Imai Y, Itoyama Y, Araki T: "Role of nitric oxide synthase against MPTP neurotoxicity in mice"Neurol Res. 24. 655-662 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Lee T-H, Kato H, Chen S-T, Kogure K, Itoyama Y: "Expression disparity of brain-derived neurotrophic factor immunoreactivity and mRNA in ischemic hippocampal neurons"NeuroReport. 13. 2271-2275 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato H, Araki T, Imai Y, Takahashi A, Itoyama Y: "Protection of dopaminergic neurons with a novel astrocyte modulating agent (R)-(-)-2-propyloctanoic acid (ONO-2506) in an MPTP-mouse model of Parkinson's disease"J Neurol Sci. in press.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato H, Takahashi A, Itoyama Y: "Cell cycle protein expression in proliferating microglia and astrocytes following transient global cerebral ischemia in the rat"Brain Res Bull. in press.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato H, Takahashi A, Itoyama Y: "Microglial proliferation and cell cycle protein upregulation in the rat hippocampus following forebrain ischemia In: Buchan A, Ito U, eds,"Maturation Phenomenon in Cerebral Ischemia V Springer-Verlag, Berlin. in press.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato H, Araki T, Imai Y, Takahashi A, Itoyama Y: "Neuroprotection by NOS inhibitors and MAO inhibitors in a mouse model of Parkinson's disease (Japaness)"Prog Med (Japanese). 22. 206-211 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurosaki R, Araki T, Kato H, Kimura S: "Experimental studies in a mouse model of Parkinson's disease (Japaness)"Prog Med (Japanese). 22. 2894-2900 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato H: "The Localization and postischemic changes in an immunophilin, FK506 binding protein-12. In: Akaike N, et al., eds, Elucidation of Brain Function (Japaness)"The main stream of Neuroscience Gaiya Shuppan-kai. 267-273 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato H, Akaike N, et al., eds: "The main stream of Neuroscience Gaiya Shuppan-kai (Japaness)"The Localization and postischemic changes in an immunophilin, FK506 binding protein-12. Elucidation of Brain Function. 267-273 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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