Document Detail


Impact of dopamine to serotonin cell ratio in transplants on behavioral recovery and L-DOPA-induced dyskinesia.
MedLine Citation:
PMID:  21600983     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Joanna García; Thomas Carlsson; Máté Döbrössy; Guido Nikkhah; Christian Winkler
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-13
Journal Detail:
Title:  Neurobiology of disease     Volume:  -     ISSN:  1095-953X     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9500169     Medline TA:  Neurobiol Dis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Inc.
Affiliation:
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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