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Serotonin neuron transplants exacerbate L-DOPA-induced dyskinesias in a rat model of Parkinson's disease

Carlsson, Thomas LU ; Carta, Manolo LU ; Winkler, Christian LU ; Björklund, Anders LU and Kirik, Deniz LU (2007) In Journal of Neuroscience 27(30). p.8011-8022
Abstract
Clinical trials in patients with Parkinson's disease have shown that transplants of fetal mesencephalic dopamine neurons can form a new functional innervation of the host striatum, but the clinical benefits have been highly variable: some patients have shown substantial recovery in motor function, whereas others have shown no improvement and even a worsening in the 3,4-dihydroxyphenyl-L-alanine (L-DOPA)-induced dyskinetic side effects. Differences in the composition of the grafted cell preparation may contribute to these discrepancies. In particular, the number of serotonin neurons contained in the graft can vary greatly depending on the dissection of the fetal tissue. Importantly, serotonin neurons have the ability to store and release... (More)
Clinical trials in patients with Parkinson's disease have shown that transplants of fetal mesencephalic dopamine neurons can form a new functional innervation of the host striatum, but the clinical benefits have been highly variable: some patients have shown substantial recovery in motor function, whereas others have shown no improvement and even a worsening in the 3,4-dihydroxyphenyl-L-alanine (L-DOPA)-induced dyskinetic side effects. Differences in the composition of the grafted cell preparation may contribute to these discrepancies. In particular, the number of serotonin neurons contained in the graft can vary greatly depending on the dissection of the fetal tissue. Importantly, serotonin neurons have the ability to store and release dopamine, formed from exogenously administered L-DOPA. Here, we have evaluated the effect of transplants containing serotonin neurons, or a mixture of dopamine and serotonin neurons, on L-DOPA-induced dyskinesias in 6-hydroxydopamine-lesioned animals. As expected, dopamine neuron-rich grafts induced functional recovery, accompanied by a 60% reduction in L-DOPA-induced dyskinesia that developed gradually over the first 10 weeks. Rats with serotonin-rich grafts with few dopamine neurons, in contrast, showed a progressive worsening of their L-DOPA-induced dyskinesias over time, and no functional improvement. The antidyskinetic effect of dopamine-rich grafts was independent of the number of serotonin neurons present. We conclude that serotonin neurons in the grafts are likely to have a detrimental effect on L-DOPA-induced dyskinesias in cases in which the grafts contain no or few dopamine neurons. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ventral mesenchephalon, levodopa, dopamine, cell grafting, 5-hydroxytryptamine, 6-hydroxydopamine
in
Journal of Neuroscience
volume
27
issue
30
pages
12 pages
publisher
Society for Neuroscience
external identifiers
  • wos:000248484800013
  • scopus:34547484764
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.2079-07.2007
language
English
LU publication?
yes
id
db54f09d-03f8-47ad-bd22-79f75bac0ccb (old id 691650)
date added to LUP
2007-12-05 15:56:55
date last changed
2017-11-19 04:12:40
@article{db54f09d-03f8-47ad-bd22-79f75bac0ccb,
  abstract     = {Clinical trials in patients with Parkinson's disease have shown that transplants of fetal mesencephalic dopamine neurons can form a new functional innervation of the host striatum, but the clinical benefits have been highly variable: some patients have shown substantial recovery in motor function, whereas others have shown no improvement and even a worsening in the 3,4-dihydroxyphenyl-L-alanine (L-DOPA)-induced dyskinetic side effects. Differences in the composition of the grafted cell preparation may contribute to these discrepancies. In particular, the number of serotonin neurons contained in the graft can vary greatly depending on the dissection of the fetal tissue. Importantly, serotonin neurons have the ability to store and release dopamine, formed from exogenously administered L-DOPA. Here, we have evaluated the effect of transplants containing serotonin neurons, or a mixture of dopamine and serotonin neurons, on L-DOPA-induced dyskinesias in 6-hydroxydopamine-lesioned animals. As expected, dopamine neuron-rich grafts induced functional recovery, accompanied by a 60% reduction in L-DOPA-induced dyskinesia that developed gradually over the first 10 weeks. Rats with serotonin-rich grafts with few dopamine neurons, in contrast, showed a progressive worsening of their L-DOPA-induced dyskinesias over time, and no functional improvement. The antidyskinetic effect of dopamine-rich grafts was independent of the number of serotonin neurons present. We conclude that serotonin neurons in the grafts are likely to have a detrimental effect on L-DOPA-induced dyskinesias in cases in which the grafts contain no or few dopamine neurons.},
  author       = {Carlsson, Thomas and Carta, Manolo and Winkler, Christian and Björklund, Anders and Kirik, Deniz},
  issn         = {1529-2401},
  keyword      = {ventral mesenchephalon,levodopa,dopamine,cell grafting,5-hydroxytryptamine,6-hydroxydopamine},
  language     = {eng},
  number       = {30},
  pages        = {8011--8022},
  publisher    = {Society for Neuroscience},
  series       = {Journal of Neuroscience},
  title        = {Serotonin neuron transplants exacerbate L-DOPA-induced dyskinesias in a rat model of Parkinson's disease},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.2079-07.2007},
  volume       = {27},
  year         = {2007},
}