期刊
YEAR IN NEUROLOGY 2
卷 1184, 期 -, 页码 55-67出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1749-6632.2009.05229.x
关键词
fetal tissue transplantation; Parkinson's disease; dopaminergic phenotype; alpha-synuclein; ubiquitin; thioflavin-s
Although fetal nigral transplants have been shown to survive grafting into the striatum, increased [F-18]6-fluroro-L-3,4-dibydroxyphenylalanine (F-18-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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