title: Correlation between decreased motor activity and dopaminergic degeneration in the ventrolateral putamen in monkeys receiving repeated MPTP administrations: a positron emission tomography study.
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 D(2) receptors were measured by positron emission tomography (PET) using [(11)C]PE2I and [(11)C]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 D(2) 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.
authors.affiliation: Department of Molecular Neuroimaging, Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nagai
authors.forename: Takafumi
authors.initials: T
authors.lastname: Minamimoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.forename: Shigeru
authors.initials: S
authors.lastname: Obayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Ito
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage*; D000818:Animals; D059290:Dopaminergic Neurons / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000502:physiology; D008252:Macaca fascicularis; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000502:physiology
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine