Loss of Parvalbumin-Positive Neurons From the Globus Pallidus in Animal Models of Parkinson Disease

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 < 0.05), which specifically affected the PV+ sub-population. A similar trend was observed in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. Markers of GABAergic activity (GAD65 and GAD67 mRNA) were not different from those of controls in 6-OHDA-lesioned rats. Taken together, these findings provide evidence for nondopaminergic neuronal cell loss in the basal ganglia of 6-OHDA-lesioned 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 hyper-activity of this nucleus despite the absence of gross alterations in GAD mRNA expression.