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• W1996231844 endingPage "587" @default.
• W1996231844 startingPage "576" @default.
• W1996231844 abstract "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." @default.
• W1996231844 created "2016-06-24" @default.
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• W1996231844 date "2011-09-01" @default.
• W1996231844 modified "2023-10-17" @default.
• W1996231844 title "Impact of dopamine to serotonin cell ratio in transplants on behavioral recovery and L-DOPA-induced dyskinesia" @default.
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• W1996231844 doi "https://doi.org/10.1016/j.nbd.2011.05.004" @default.
• W1996231844 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21600983" @default.
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