| Project/Area Number |
14570596
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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 | Okayama University |
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Principal Investigator |
ASANUMA Masato Okayama University, Graduate School of Medicine and Dentistry, Dept.of Brain Science, Associate Professor, 大学院・医歯学総合研究科, 助教授 (00273970)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Ikuko Okayama University, Graduate School of Medicine and Dentistry, Dept.of Brain Science, Research Associate, 大学院・医歯学総合研究科, 助手 (40335633)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | PARKINSON'S DISEASE / MELANOCYTE / TYROSINASE / CELL TRANSPLANTATION / PRIMARY CULTURE / DOPAMINE / BASAL GANGLIA / MELANOMA |
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| Research Abstract |
To investigate the possible effects of tyrosinase-producing cell transplantation in parkinsonian models, we performed intrastriatal transplantation of melanocytes or melanoma cells, as tyrosinase-producing cells, into hemi-parkinsonian model animals, as follows :
1.Transplantation of melanoma cells into the striatum of parkinsonian models
Intrastriatal transplantation of B16-F1 melanoma cells, as tyrosinase-producing cells, into hemi-parkinsonian rats lesioned by 6-OHDA markedly ameliorated apomorphine-induced rotation behavior towards contralateral side up to 40 days after the transplantation of melanoma cells, coinciding with expression of dopamine-positive signals around survived transplant.
2.Primary cultured melanocvtes from the back of newborn mice
We established the procedure of primary culture for melanocytes from the back of newborn C57BL mice, which showed higher tyrosinase activity than melanocytes from albino mice.
3.Transplantation of primary_cultured melanocytes into the stria
… More
tum of parkinsonian models
The transplantation of primary cultured melanocytes from the back of newborn black mice into the lesioned striatum of hemi-parkinsonian mice markedly and continuously ameliorated the apomorphine-induced contralateral rotation behavior up to 3 months after the melanocyte transplantation. In the transplanted group with melanocytes, the striatal transplant melanocytes survived coinciding with dopamine- and tyrosinase-positive signals along the transplant in the striatum 3 months after the transplantation.
4.Primary cultured melanocytes from the adult mice
We tried to establish the culture of melanocytes from the back skin of adult C57BL mice for future auto-transplantation of melanocytes into parkinsonian models, but failed to do it because of contamination of the folliculi.
5.Distribution of tyrosinase-positive cells in the brain of parkinsonian models
Tyrosinase constitutively expressed mainly on oligodendrocytes in the corpus callosum, striatum and substantia nigra. In the parkinsonian model mice, tyrosinase-positive oligodendrocytes increased in the striatum, whereas it decreased in the substantia nigra.
These experimental results suggest a therapeutic potency of tyrosinase-producing cells such as melanocytes which may complement tyrosine hydroxylase when dopaminergic neurons are degenerated in Parkinson's disease, and may normalize L-DOPA-induced abnormal dopamine turnover Less
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