| Impact of dopamine to serotonin cell ratio in transplants on behavioral recovery and L-DOPA-induced dyskinesia. | |
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MedLine Citation:
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PMID: 21600983 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Fetal dopamine (DA) cell transplantation has shown to be efficient in reversing behavioral impairments associated with Parkinson's disease. However, the beneficial effects on motor behavior and L-DOPA-induced dyskinesia have varied greatly in between clinical trials and patients within the same trial. Recently, the inclusion of serotonin (5-HT) neurons in the grafted tissue has been suggested to play an important negative role, in particular, on the effect of L-DOPA-induced dyskinesia. In the present study we have evaluated the influence of different ratios of DA neurons in relation to 5-HT neurons in the graft on spontaneous motor behavior and L-DOPA-induced dyskinesia in a rat model of Parkinson's disease. We show that using the standard dissection method that gives rise to a DA:5-HT ratio in the graft of 2:1 to 1:2 there is significant and consistent improvement in spontaneous motor behavior and reversal of L-DOPA-induced dyskinesia. Increasing the ratio of 5-HT neurons in the graft, to a DA:5-HT ratio of in between 1:3 and 1:10, still induces significant reduction of L-DOPA-induced dyskinesia, suggesting that the detrimental effect of 5-HT neurons on L-DOPA-induced dyskinesia is prevented even by small numbers of DA neurons in the graft. Nonetheless, while the post-synaptic responses were normalized following peripheral L-DOPA delivery in animals with low DA:5-HT ratio, we observed a pharmacological indication of hyperactive pre-synaptic response in these animals. These data suggests that 5-HT cells within a graft are neither detrimental nor beneficial for functional effects of DA-rich transplants; however, in absence of sufficient numbers of DA neurons, the 5-HT neurons may induce negative effects following L-DOPA therapy. In summary, our data indicate that for future clinical trials the inclusion of 5-HT neurons in grafted tissue is not critical as long as there are sufficient numbers of DA cells in the graft. |
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Authors:
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Joanna García; Thomas Carlsson; Máté Döbrössy; Guido Nikkhah; Christian Winkler |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-13 |
Journal Detail:
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Title: Neurobiology of disease Volume: - ISSN: 1095-953X ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-5-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9500169 Medline TA: Neurobiol Dis Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier Inc. |
Affiliation:
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Department of Neurology, University Hospital Freiburg, 79106 Freiburg, Germany; Department of Stereotactic Neurosurgery, Laboratory of Molecular Neurosurgery, University Hospital Freiburg, 79106 Freiburg, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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