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Neurobiol Dis. 2011 Sep;43(3):552-7. doi: 10.1016/j.nbd.2011.05.001. Epub 2011 May 12.

Transfer of host-derived α synuclein to grafted dopaminergic neurons in rat.

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  • 1Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA. jkordowe@rush.edu

Abstract

Multiple laboratories have recently demonstrated that long-term dopaminergic transplants form Lewy bodies in patients with Parkinson's disease. Debate has arisen as to whether these Lewy bodies form from the transfer of α synuclein from the host to the graft or whether they form from intrinsic responses of the graft from being placed into what was, or became, an inflammatory focus. To test whether the former hypothesis was possible, we grafted fetal rat ventral mesencephalon into the dopamine depleted striatum of rats that had previously received 6-hydroxydopamine lesions. One month after the transplant, rats received viral over expression of human α synuclein (AAV2/6-α synuclein) or green fluorescent protein (AAV2/6-GFP) into the striatum rostral to the grafts. Care was taken to make sure that the AAV injections were sufficiently distal to the graft so no cells would be directly transfected. All rats were sacrificed five weeks after the virus injections. Double label immunohistochemistry combined with confocal microscopy revealed that a small number of grafted tyrosine hydroxylase (TH) neurons (5.7% ± 1.5% (mean ± SEM) of grafted dopamine cells) expressed host derived α synuclein but none of the grafted cells expressed host-derived GFP. The α synuclein in a few of these cells was misfolded and failed to be digested with proteinase K. These data indicate that it is possible for host derived α synuclein to transfer to grafted neurons supporting the concept that this is one possible mechanism by which grafted dopamine neurons form Lewy bodies in Parkinson's disease patients.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
21600984
[PubMed - indexed for MEDLINE]
PMCID:
PMC3430516
Free PMC Article

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