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Lewy body pathology in fetal grafts.

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.
AuthorsYaping Chu, Jeffrey H Kordower
JournalAnnals 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
PMID20146690 (Publication Type: Journal Article, Review)
Chemical References
  • Dopamine Plasma Membrane Transport Proteins
  • Fluorine Radioisotopes
  • Melanins
  • alpha-Synuclein
  • neuromelanin
  • fluorodopa F 18
  • Dihydroxyphenylalanine
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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