Changes in dopamine availability in the nigrostriatal and mesocortical dopaminergic systems by gait in Parkinson's disease.
The basal ganglia play a role in controlling movement during gait. The aim of the present study was to investigate changes in dopamine transporter (DAT) availability in the striatum and extrastriatal region in association with walking exercise in six normal subjects and seven age-matched unmedicated patients with Parkinson's disease. This was done by comparing DAT radioligand uptake in the dopaminergic projection areas after gait with that under the resting condition using a DAT probe, 11C-labelled 2-beta-carbomethoxy-3beta-(4-fluorophenyl) tropane ([11C]CFT) and PET. Physiological parameters were stable during and after gait in both groups. The regions of interest method for measuring differences in [11C]CFT uptake level and voxel-based statistical parametric mapping (SPM96) showed that [11C]CFT uptake in the striatum (specifically the putamen) was decreased by gait to a greater extent in normal subjects, whereas a significant reduction in [11C]CFT uptake was not found in the putamen but in the caudate and orbitofrontal cortex in Parkinson's disease patients. These results are the first in vivo evidence that DAT availability is reduced in the nigrostriatal projection area by basic human behaviour, i.e. gait. Alterations in this availability in Parkinson's disease suggested that shifted activation in the medial striatum and the mesocortical dopaminergic system might reflect the pathophysiology of parkinsonian gait.
Ouchi
Y
Y
Positron Medical Center, Hamakita Japan.
Kanno
T
T
Okada
H
H
Yoshikawa
E
E
Futatsubashi
M
M
Nobezawa
S
S
Torizuka
T
T
Tanaka
K
K
D000368:Aged; D001158:Arteries; D001794:Blood Pressure; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000493:pharmacokinetics; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D005684:Gait; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000378:metabolism*; D006339:Heart Rate; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000378:metabolism*; D014055:Tomography, Emission-Computed; D016138:Walking
D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine; D004298:Dopamine