Project/Area Number |
01480127
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Research Category |
Grant-in-Aid for General Scientific Research (B)
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Allocation Type | Single-year Grants |
Research Field |
Neurophysiology and muscle physiology
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Research Institution | Nagoya City University |
Principal Investigator |
NISHINO Hitoo Nagoya City University Medical School, Department of Physiology, Professor, 医学部, 教授 (60073730)
|
Co-Investigator(Kenkyū-buntansha) |
HASHITANI Takeshi Nagoya City University Medical School, Department of Physiology, Instructor, 医学部, 助手 (30172852)
ISOBE Yoshiaki Nagoya City University Medical School, Department of Physiology, Instructor, 医学部, 助手 (70094357)
FURUYAMA Fujiya Nagoya City University Medical School, Department of Physiology, Instructor, 医学部, 助手 (00080101)
|
Project Period (FY) |
1989 – 1990
|
Project Status |
Completed (Fiscal Year 1990)
|
Budget Amount *help |
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1990: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1989: ¥5,700,000 (Direct Cost: ¥5,700,000)
|
Keywords | neuronal grafting / Parkinson's disease / dopamine / trophic factor / Phenotypic plasticity / striatum / substantia nigra / 移植 / カテコラミン / 表現型 / レセプタ- / mRNA / タンパク |
Research Abstract |
1. Using model rats of hemi-parkinson's disease, the mechanisms of functional recovery after grafting of dopaminergic cells were investigated. We found : 1) the survival of TH mRNA/TH positive cells, 2) increase of dopamine synthesis/release, 3) synaptic connections, 4) recovery of dopamine transporter and 5) normalization of D_1 and D_2 receptor-bindings. 2. Bovine total ganglioside (tGS), sialosyl cholesterol (ganglioside analogue), IL-6 (B cell stimulating cytokine) facilitated the development/growth of grafted dopaminergic cells, and promoted the motor recovery. 3.1) grafted chromaffin (adrenergic) cells transmute to dopaminergic neurons in dopamine-depleted striatum, 2) grafted noradrenergic cells transmute to dopaminergic cells in dopa-mine-depleted striatum but not in the lateral ventricle, 3) dopaminergic neurons grow much better in dopamine-depleted striatum than in normal striatum or the cortex, 4) grafted cholinergic neurons grow in a similar fashion in normal and dopamine-depleted striatum, 5) co-cultured midbrain neurons (partly dopaminergic neurons) extend more neurites faster toward the dopamine-depleted than toward the intact striatal tissue. These evidences suggest the increase in synthesis/release of some trophic factors for dopaminergic neurons in dopamine-depleted striatum. 4. In soluble fraction of dopamine-depleted striatal tissue a few acidic proteins increased. The purification/identification of these proteins is under way.
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