| Project/Area Number |
10670615
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Tokyo Metropolitan Institution for Medical Research (1999-2000)
Tokyo Metropolitan Institute for Neuroscience (1998) |
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Principal Investigator |
NISHI Katsunori Department of Neurology, Tokyo Metropolitan Institution for Neuroscience, Staff Scientist, Director, 東京都神経科学総合研究所, 副参事研究員 (00138257)
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| Co-Investigator(Kenkyū-buntansha) |
MIWA Hideto Department of Neurology, Juntendo University School of Medicine, Assistant Professor, 医学部, 講師 (50231626)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | MPTP / dopaminergic neuron / c-jun / Parkinson's disease / 培養 |
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| Research Abstract |
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin which selectively affects nigro-striatal dopaminergic neurons in man, primates, and several other species including mice, and has been extensively studied as an experimental model of parkinsonism. Several possible mechanisms of neuronal toxicity leading to cell death, have been proposed including mitochondrial respiratory failure, oxidative stress and NMDA receptor-mediated cytotoxicity. Despite intensive studies, the precise mechanism underlying the cytotoxicity of MPP^+ against dopaminergic neurons remains unclear. In the previous study, we found long lasting expression of c-Jun and negative in situ end labeling (TUNEL) following administration of 1-methyl-4-phenylpyridinium (MPP^+). These results suggested the existence of some cascade mechanism of non-apoptotic type cell death in in dopaminergic neurons. The c-Jun transcription factor is regarded as a pivotal regulator for neuronal death or survival. We pre-administered c-jun antisense oligonucleotide into MPP^+-treated ventral mesencephalic culture in order to determine whether the down-regulation of c-Jun play a significant role in the rescue mechanism in severely stressed dopaminergic neurons. With the administration of antisense oligonucleutide, dopaminergic neuronal death was attenuated slightly. This may suggest that the long lasting expression of c-Jun is acting to kill these neurons. The precise mechanism by which this transcription factor killing neurons requires further study.
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