1. Impact of dopamine versus serotonin cell transplantation for the development of graft-induced dyskinesia in a rat Parkinson model.
- Author
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García J, Carlsson T, Döbrössy M, Nikkhah G, and Winkler C
- Subjects
- Adrenergic Agents toxicity, Amphetamines pharmacology, Analysis of Variance, Animals, Antiparkinson Agents adverse effects, Central Nervous System Stimulants pharmacology, Disease Models, Animal, Dyskinesias pathology, Female, Functional Laterality, Levodopa adverse effects, Nerve Fibers pathology, Oxidopamine toxicity, Parkinson Disease drug therapy, Parkinson Disease etiology, RNA-Binding Proteins metabolism, Rats, Rats, Sprague-Dawley, Statistics as Topic, Stereotyped Behavior drug effects, Tyrosine 3-Monooxygenase metabolism, Cell Transplantation adverse effects, Dopaminergic Neurons physiology, Dyskinesias etiology, Parkinson Disease surgery, Serotonergic Neurons physiology
- Abstract
Graft-induced dyskinesia (GID), covering a range of dystonic and choreiform involuntary movements, has been observed in some patients with Parkinson's disease (PD) after intracerebral cell transplantation. These dyskinesias have been severe in a number of patients and represent one of the main obstacles for further development of the cell therapy in PD. Serotonin neurons, included into the dopaminergic cell suspension due to the nature of the dissection process, have been suggested as a key factor for the development of GID, since the administration of the serotonin (5-HT)(1A)-receptor agonist buspirone reduced dyskinesia in transplanted PD patients. In the present study, we characterized GID in the rat PD model after transplantation of dopaminergic grafts containing different amounts of serotonin neurons. The severity of GID was significantly correlated with the amount of grafted dopamine and serotonin neurons, but the r-values were low. However, neither the innervation density of dopamine and serotonin fibers in the grafted striatum nor the dopamine-to-serotonin cell ratio correlated significantly with the severity of GID. The results extend prior knowledge of the role of dopaminergic grafts in the development of GID and show that, in the animal model, serotonin neurons within the graft suspension might be involved, but given sufficient dopamine cells, their impact on GID may be minor., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2012
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