title: Impact of dopamine versus serotonin cell transplantation for the development of graft-induced dyskinesia in a rat Parkinson model.
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.
authors: Department of Neurology, University Hospital Freiburg, Breisacher Strasse 64, 79106 Freiburg, Germany.
authors: Joanna
authors: J
authors: García
authors: Thomas
authors: T
authors: Carlsson
authors: Máté
authors: M
authors: Döbrössy
authors: Guido
authors: G
authors: Nikkhah
authors: Christian
authors: C
authors: Winkler
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000662:Amphetamines / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects; D017690:Cell Transplantation / Q000009:adverse effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000502:physiology*; D020820:Dyskinesias / Q000209:etiology* / Q000473:pathology; D005260:Female; D007839:Functional Laterality; D007980:Levodopa / Q000009:adverse effects; D009412:Nerve Fibers / Q000473:pathology; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology / Q000601:surgery*; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D059326:Serotonergic Neurons / Q000502:physiology*; D013223:Statistics as Topic; D013239:Stereotyped Behavior / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D000662:Amphetamines; D000978:Antiparkinson Agents; D000697:Central Nervous System Stimulants; D016601:RNA-Binding Proteins; C482440:Sert1 protein, rat; D007980:Levodopa; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase