Focal not widespread grafts induce novel dyskinetic behavior in parkinsonian rats

Eleonora Maries, Jeffrey H. Kordower, Yaping Chu, Timothy J. Collier, Caryl E. Sortwell, Eliza Olaru, Kathleen Shannon, Kathy Steece-Collier

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)165-180
Number of pages16
JournalNeurobiology of Disease
Volume21
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

Keywords

  • Dopamine neuron grafting
  • Dyskinesias
  • FosB/ΔFosB transcription factors
  • Levodopa
  • Rats

ASJC Scopus subject areas

  • Neurology

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