Lewy body pathology in fetal grafts

Research output: Chapter in Book/Report/Conference proceedingChapter

71 Scopus citations

Abstract

Although fetal nigral transplants have been shown to survive grafting into the striatum, increased [18F]6-fluroro-L-3,4-dihydroxyphenylalanine (18F-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 α-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 α-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.

Original languageEnglish (US)
Title of host publicationThe Year in Neurology 2
PublisherBlackwell Publishing Inc.
Pages55-67
Number of pages13
ISBN (Print)9781573317801
DOIs
StatePublished - Jan 2010
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1184
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Dopaminergic phenotype
  • Fetal tissue transplantation
  • Parkinson's disease
  • Thioflavin-s
  • Ubiquitin
  • α-Synuclein

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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