Lewy body pathology in fetal grafts
Identifieur interne : 002347 ( Main/Curation ); précédent : 002346; suivant : 002348Lewy body pathology in fetal grafts
Auteurs : Yaping Chu [États-Unis] ; Jeffrey H. Kordower [États-Unis]Source :
- Annals of the New York Academy of SciencesThe Year in Neurology 2 [ 0077-8923 ] ; 2010-01.
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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.
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DOI: 10.1111/j.1749-6632.2009.05229.x
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<front><div type="abstract" xml:lang="en">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.</div>
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