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

J Parkinsons Dis. 2011;1(4):347-57. doi: 10.3233/JPD-2011-11068.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Antiparkinson Agents / adverse effects
  • Autoradiography
  • Basal Ganglia / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dyskinesia, Drug-Induced / pathology
  • Female
  • Humans
  • Levodopa / adverse effects
  • Male
  • Neurons / metabolism
  • Parkinson Disease / drug therapy
  • Parkinson Disease / pathology
  • Postmortem Changes
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Putamen / metabolism*
  • Putamen / pathology
  • Up-Regulation / drug effects
  • Up-Regulation / physiology*

Substances

  • Antiparkinson Agents
  • Dopamine Plasma Membrane Transport Proteins
  • FOSB protein, human
  • Proto-Oncogene Proteins c-fos
  • Levodopa