| Project/Area Number |
62570054
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurophysiology and muscle physiology
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| Research Institution | Nagoya City University Medical School (1988)
Toyama Medical and Pharmaceutical University (1987) |
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Principal Investigator |
NISHINO Hitoo Department of Physiology, Nagoya City University Medical School, 医学部第二生理学, 教授 (60073730)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIJO Hisao Department of Physiology, Faculty of Medicine, Toyama Medical and Pharmaceutical, 医学部第二生理学, 助手 (00189284)
NAKAMURA Kiyomi Department of Physiology, Faculty of Medicine, Toyama Medical and Pharmaceutical, 医学部第二生理学, 助手 (20143860)
ONO Taketoshi Department of Physiology, Faculty of Medicine, Toyama Medical and Pharmaceutical, 医学部第二生理学, 教授 (50019577)
HASHITANI Takeshi Department of Physiology, Nagoya City University Medical School, 医学部第二生理学, 助手 (30172852)
ISOBE Yoshiaki Department of Physiology, Nagoya City University Medical School, 医学部第二生理学, 助手 (70094357)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1988: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1987: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Transplantation / Dopamine / Chromaffin cell / Parkinson's disease / Caudate / Differentiation / Plasticity / ラット / ドーパミング / 栄養因子 / Ca電流 |
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| Research Abstract |
Catecholaminergic cells (dopaminergic, noradrenergic and chromaffin cells) were transplanted into rats with unilateral 6-OHDA lesion in nigrostriatal dopamine pathway, and recovery of motor disturbance, cell growth, dopamine turnover, and effect of ganglioside were investigated.
1. Motor recovery was observed in more than 90% of animals following dopaminergic cell grafting. many tyrosine hydroxylase (TH) positive cells survived around the grafting track and made synaptic contacts with host neuronal elements. Using microdialysis it was found that dopamine recovered up to almost control level and DOPAC and HVA to one third of controls. 2. Following grafting of locus coeruleus noradrenergic neurons, motor recovery was observed in about 40% of animals. A fewer TH positive-, dopamine beta hydroxylase (DBH) negative cells survived only on the margin of the track. Motor recovery was correlated with the length of time between 6-OHDA lesion and grafting. Dopamine recovered up to 50% and DOPAC and HVA to one third of control levels. Thus it is suggested that some trophic factor that promotes the differentiation of noradrenergic cells into dopaminergic cells develops and fluctuates in dopamine denervated caudate. 3. Less than 30% of animals showed motor recovery after grafting of chromaffin cells. Local or systemic administration of nerve growth factor, interleukin-6 and ganglioside had no effect on the recovery. To improve the cell survival and motor recovery it is necessary to modulate the microenvironment of the grafted cells i. e. , activation of astroglia or increase of endogenous trophic factors. Such study is under way. 4. Ganglioside facilitated the development of grafted dopaminergic cells and motor recovery, and thus could be one of a strong candidate for CNS tropic factor.
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