title: No differential regulation of dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) binding in a primate model of Parkinson disease.
abstract: Radioligands for DAT and VMAT2 are widely used presynaptic markers for assessing dopamine (DA) nerve terminals in Parkinson disease (PD). Previous in vivo imaging and postmortem studies suggest that these transporter sites may be regulated as the numbers of nigrostriatal neurons change in pathologic conditions. To investigate this issue, we used in vitro quantitative autoradioradiography to measure striatal DAT and VMAT2 specific binding in postmortem brain from 14 monkeys after unilateral internal carotid artery infusion of 1-Methyl-4-Phenyl-1,2,3,6-tetrahydropyridine (MPTP) with doses varying from 0 to 0.31 mg/kg. Quantitative estimates of the number of tyrosine hydroxylase (TH)-immunoreactive (ir) neurons in substantia nigra (SN) were determined with unbiased stereology, and quantitative autoradiography was used to measure DAT and VMAT2 striatal specific binding. Striatal VMAT2 and DAT binding correlated with striatal DA (r(s) = 0.83, r(s) = 0.80, respectively, both with n = 14, p<0.001) but only with nigra TH-ir cells when nigral cell loss was 50% or less (r = 0.93, n = 8, p = 0.001 and r = 0.91, n = 8, p = 0.002 respectively). Reduction of VMAT2 and DAT striatal specific binding sites strongly correlated with each other (r = 0.93, n = 14, p<0.0005). These similar changes in DAT and VMAT2 binding sites in the striatal terminal fields of the surviving nigrostriatal neurons demonstrate that there is no differential regulation of these two sites at 2 months after MPTP infusion.
authors.affiliation: Department of Neurology, Washington University, St. Louis, Missouri, United States of America.
authors.forename: LinLin
authors.initials: L
authors.lastname: Tian
authors.forename: Morvarid
authors.initials: M
authors.lastname: Karimi
authors.forename: Susan K
authors.initials: SK
authors.lastname: Loftin
authors.forename: Chris A
authors.initials: CA
authors.lastname: Brown
authors.forename: HuChuan
authors.initials: H
authors.lastname: Xia
authors.forename: JinBin
authors.initials: J
authors.lastname: Xu
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mach
authors.forename: Joel S
authors.initials: JS
authors.lastname: Perlmutter
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D003342:Corpus Striatum; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D000882:Haplorhini; D009474:Neurons; D010300:Parkinson Disease / Q000378:metabolism*; D013378:Substantia Nigra; D014446:Tyrosine 3-Monooxygenase; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase