Lewy body pathology in fetal grafts.

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
  • 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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: