Article ID Journal Published Year Pages File Type
4351511 Neuroscience Research 2012 7 Pages PDF
Abstract

Parkinson's disease (PD) patients have remarkably reduced levels of dopaminergic biomarkers in the caudal putamen. However, the relationship between motor impairments and the localization of intrastriatal dopaminergic degeneration in monkey PD models remains unclear. To identify the striatal areas with dopaminergic dysfunction responsible for motor impairments, we measured changes in both general motor activity and in vivo dopaminergic biomarkers in three cynomolgus monkeys that repeatedly received 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), starting in the normal state and continuing until after tremor appearance. Binding of dopamine transporters (DAT) and D2 receptors were measured by positron emission tomography (PET) using [11C]PE2I and [11C]raclopride, respectively. Region-of-interest-based regression analysis demonstrated the degree of general motor activity reduction to be explained by striatal DAT binding but not by D2 receptor binding. Furthermore, voxel-based analysis revealed a significant correlation between reduced general motor activity and decreased DAT binding, specifically in the ventrolateral putamen, which corresponds to the area receiving upper body motor inputs from the primary motor cortex. These results suggest that specific functional deficits in PD models are closely related to the degeneration of dopaminergic terminals in the striatal subregion responsible for these functions and that the level of deficit is dependent on the degree of degeneration.

► We assess general motor activity and dopaminergic biomarkers in MPTP-treated monkeys. ► General motor activity in monkeys progressively reduced by repeated MPTP treatments. ► Striatal dopamine transporter (DAT) binding explains general motor activity reduction. ► The activity significantly correlates DAT binding in the ventrolateral putamen.

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