Putaminal upregulation of FosB/ΔFosB-like immunoreactivity in Parkinson's disease patients with Dyskinesia

H. S. Lindgren, D. Rylander, H. Iderberg, Micael Andersson, Sean O'Sullivan, D. R. Williams, A. J. Lees, M. A. Cenci

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Abstract

The transcription factor ΔFosB is a mediator of maladaptive neuroplasticity in animal models of Parkinson's disease (PD) and L-DOPA-induced dyskinesia. Using an antibody that recognizes all known isoforms of FosB and ΔFosB, we have examined the expression of these proteins in post-mortem basal ganglia sections from PD patients. The patient cases were classified as being dyskinetic or non-dyskinetic based on their clinical records. Sections from neurologically healthy controls were also included in the study. Compared to both controls and non-dyskinetic cases, the dyskinetic group showed a higher density of FosB/ΔFosB-immunopositive cells in the posterior putamen, which represents the motor region of the striatum in primates. In contrast, the number of FosB/ΔFosB-positive cells did not differ significantly among the groups in the caudate, a region primarily involved with the processing of cognitive and limbic-related information. Only sparse FosB/ΔFosB immunoreactivity was found in the in the pallidum externum and internum, and no significant group differences were detected in these nuclei. The putaminal elevation of FosB/ΔFosB-like immunoreactivity in patients who had been affected by L-DOPA-induced dyskinesia is consistent with results from both rat and non-human primate models of this movement disorder. The present findings support the hypothesis of an involvement of ΔFosB-related transcription factors in the molecular mechanisms of L-DOPA-induced dyskinesia.

Original languageEnglish
Pages (from-to)347-357
Number of pages11
JournalJournal of Parkinson's Disease
Volume1
Issue number4
DOIs
Publication statusPublished - 1 Dec 2011

Keywords

  • dopaminergic therapies
  • immediate-early genes
  • medium-spiny neurons
  • Motor complications
  • neurodegeneration
  • striatonigral
  • striatopallidal

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