TY - JOUR
T1 - Focal not widespread grafts induce novel dyskinetic behavior in parkinsonian rats
AU - Maries, Eleonora
AU - Kordower, Jeffrey H.
AU - Chu, Yaping
AU - Collier, Timothy J.
AU - Sortwell, Caryl E.
AU - Olaru, Eliza
AU - Shannon, Kathleen
AU - Steece-Collier, Kathy
N1 - Funding Information:
The authors would like to extend their gratitude to Dr. Jack Lipton (Univ. of Cincinnati Neurology) and Drs. Sue Leurgans and Joanne Wuu (Rush Biostatistics) for their assistance with statistical evaluations; Mr. Nathan Levine and Mr. Brian Daley for their excellent technical assistance; Ms. Jennifer Stancati for valuable videography and photography skills; and Dr. Sylvia Perez and Ms. Michelle Gartland for expert computer-assisted graphics. This work was funded in part by NIH NS045132 (KSC) and DoD DAMD170310623 (KSC).
PY - 2006/1
Y1 - 2006/1
N2 - 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/ΔFosB 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/ΔFosB 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.
AB - 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/ΔFosB 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/ΔFosB 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.
KW - Dopamine neuron grafting
KW - Dyskinesias
KW - FosB/ΔFosB transcription factors
KW - Levodopa
KW - Rats
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U2 - 10.1016/j.nbd.2005.07.002
DO - 10.1016/j.nbd.2005.07.002
M3 - Article
C2 - 16095907
AN - SCOPUS:29144490744
SN - 0969-9961
VL - 21
SP - 165
EP - 180
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 1
ER -