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Levodopa-induced dyskinesia in MPTP-treated macaques is not dependent on the extent and pattern of nigrostrial

Céline Guigoni1, Sandra Dovero, Incarnation Aubert

  • 1Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire, CNRS UMR 5543, Universite victor Segalen-Bordeaux, 33076 Bordeaux Cedex, France.

The European Journal of Neuroscience
|July 21, 2005
PubMed

Insights

Neither the extent nor the pattern of nigrostriatal denervation sufficiently explains levodopa-induced dyskinesia in parkinsonian monkeys. This suggests other factors contribute to this common side effect of Parkinson's disease treatment.

Area of Science:

  • Neuroscience
  • Parkinson's Disease Research
  • Pharmacology

Background:

  • Levodopa-induced dyskinesia is a common complication in Parkinson's disease treatment.
  • The role of nigrostriatal denervation extent in dyskinesia development is debated.
  • The pattern of denervation may also influence dyskinesia risk.

Purpose of the Study:

  • To investigate the relationship between nigrostriatal denervation extent and pattern and levodopa-induced dyskinesia.
  • To determine if lesion characteristics can predict dyskinesia in parkinsonian macaques.

Main Methods:

  • Studied a homogeneous population of parkinsonian macaque monkeys chronically treated with levodopa.
  • Assessed nigrostriatal denervation extent by counting tyrosine-hydroxylase (TH)-immunopositive neurons.
  • Analyzed striatal dopamine transporter (DAT) binding and TH immunostaining.
  • Quantified striatal TH content using Western blotting.
  • Examined fiber patterns using TH- and DAT-immunopositive staining.

Main Results:

  • No significant differences in the extent of nigrostriatal denervation were found between dyskinetic and non-dyskinetic animals.
  • Striatal DAT binding, TH immunostaining, and overall TH content were identical in both groups.
  • Detailed analysis revealed comparable patterns of TH- and DAT-immunopositive striatal fibers across all regions and levels.

Conclusions:

  • Neither the extent nor the pattern of nigrostriatal denervation adequately explains the occurrence of levodopa-induced dyskinesia.
  • These findings suggest that factors beyond nigrostriatal lesion characteristics are critical in the development of dyskinesia.

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