Loss of parvalbumin-positive neurons from the globus pallidus in animal models of parkinson disease

Diana Fernández-Suárez, Marta Celorrio, Jose L. Lanciego, Rafael Franco, María S. Aymerich

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16 Scopus citations

Abstract

The external segment of the globus pallidus (GPe) in humans and the equivalent structure in rodents, the globus pallidus (GP), influence signal processing in the basal ganglia under normal and pathological conditions. Parvalbumin (PV) immunoreactivity defines 2 main neuronal subpopulations in the GP/GPe: PV-immunopositive cells that project mainly to the subthalamic nucleus and the internal segment of the GP and PV-negative cells that mainly project to the striatum. We evaluated the number of neurons in the GP/GPe in animal models of Parkinson disease. In rats, dopaminergic denervation with 6-hydroxydopamine (6-OHDA) provoked a significant decrease in the number of GP neurons (12% ± 4%, p G 0.05), which specifically affected the PV+ subpopulation. A similar trend was observed in 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP)Ytreated monkeys. Markers of GABAergic activity (GAD65 and GAD67 mRNA) were not different from those of controls in 6-OHDAYlesioned rats. Taken together, these findings provide evidence for nondopaminergic neuronal cell loss in the basal ganglia of 6-OHDAYlesioned rats and suggest that a similar loss may occur in the MPTP monkey. These data suggest that in patients with Parkinson disease, the loss of GABAergic neurons projecting to the subthalamic nucleus may contribute to the hyperactivity of this nucleus despite the absence of gross alterations in GAD mRNA expression.

Original languageEnglish
Pages (from-to)973-982
Number of pages10
JournalJournal of neuropathology and experimental neurology
Volume71
Issue number11
DOIs
StatePublished - Nov 2012

Keywords

  • 6-OHDA rat
  • Basal ganglia
  • External segment
  • Globus pallidus
  • MPTP
  • Neurodegeneration
  • Parkinson disease
  • Parvalbumin
  • Primate

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