Abstract |
Although fetal nigral transplants have been shown to survive grafting into the striatum, increased [(18)F]6-fluroro- L-3,4-dihydroxyphenylalanine ((18)F-DOPA) uptake and improved motor function in open-label assessments have failed to establish any clinical benefits in double-blind, sham-controlled studies. To understand morphological and neurochemical alterations of grafted neurons, we performed postmortem analyses on six Parkinson's disease (PD) patients who had received fetal tissue transplantation 18-19 months, 4 years, and 14 years previously. These studies revealed robust neuronal survival with normal dopaminergic phenotypes in 18-month-old grafts and decreased dopamine transporter and increased cytoplasmic alpha-synuclein in 4-year-old grafts. We also found a decline of both dopamine transporter and tyrosine hydroxylase and the formation of Lewy body-like inclusions in 14-year-old grafts, which stained positive for alpha-synuclein and ubiquitin proteins. These pathological changes suggest that PD is an ongoing process that affects grafted cells in the striatum in a manner similar to how resident dopamine neurons are affected in the substantia nigra.
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Authors | Yaping Chu, Jeffrey H Kordower |
Journal | Annals of the New York Academy of Sciences
(Ann N Y Acad Sci)
Vol. 1184
Pg. 55-67
(Jan 2010)
ISSN: 1749-6632 [Electronic] United States |
PMID | 20146690
(Publication Type: Journal Article, Review)
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Chemical References |
- Dopamine Plasma Membrane Transport Proteins
- Fluorine Radioisotopes
- Melanins
- alpha-Synuclein
- neuromelanin
- fluorodopa F 18
- Dihydroxyphenylalanine
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Topics |
- Animals
- Corpus Striatum
(surgery)
- Dihydroxyphenylalanine
(analogs & derivatives, pharmacokinetics)
- Dopamine Plasma Membrane Transport Proteins
(metabolism)
- Female
- Fetal Tissue Transplantation
(pathology)
- Fetus
(pathology)
- Fluorine Radioisotopes
(pharmacokinetics)
- Graft Survival
- Humans
- Isotope Labeling
- Lewy Bodies
(pathology)
- Melanins
(metabolism)
- Pregnancy
- Substantia Nigra
(pathology, transplantation)
- alpha-Synuclein
(metabolism)
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