Focal not widespread grafts induce novel dyskinetic behavior in parkinsonian rats.
Dyskinesias are a common consequence of dopaminergic therapy in patients with Parkinson's disease. Little is known about the influence of cellular replacement strategies upon drug-induced dyskinesias. In the current study, we employed parkinsonian rats to test whether the distribution of dopamine neuron grafts could differentially alter striatal circuitry and levodopa-induced dyskinesias. Specifically, we compared behavioral and neurochemical consequences of dopamine reinnervation restricted to a focal region of the striatum to innervation encompassing the majority of the striatum by distributing the same number of cells into single locus or multiple locations. Both the single-site and widespread grafts reduced pregraft dyskinesias and normalized FosB/DeltaFosB in the dorsal two-thirds of the lateral striatum. However, single-site DA graft recipients developed a robust, novel forelimb-facial stereotypy and upregulated FosB/DeltaFosB expression in the ventrolateral striatum, an area associated with movements of tongue and forelimbs. The onset of forelimb-facial stereotypy correlated with measures of increased graft function.
Maries
Eleonora
E
Department of Neuroscience, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, N. Chicago, IL 60064, USA.
Kordower
Jeffrey H
JH
Chu
Yaping
Y
Collier
Timothy J
TJ
Sortwell
Caryl E
CE
Olaru
Eliza
E
Shannon
Kathleen
K
Steece-Collier
Kathy
K
D000818:Animals; D001522:Behavior, Animal; D016380:Brain Tissue Transplantation / Q000009:adverse effects* / Q000379:methods; D003342:Corpus Striatum / Q000601:surgery; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D020820:Dyskinesias / Q000209:etiology* / Q000503:physiopathology; D016332:Fetal Tissue Transplantation / Q000009:adverse effects* / Q000379:methods; D008297:Male; D008636:Mesencephalon / Q000637:transplantation*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000503:physiopathology / Q000601:surgery*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013565:Sympatholytics
D016760:Proto-Oncogene Proteins c-fos; D013565:Sympatholytics; D016627:Oxidopamine; D004298:Dopamine