Changes in dopamine availability in the nigrostriatal and mesocortical dopaminergic systems by gait in Parkinson's disease

• Published in: Brain (London, England : 1878) Vol. 124; no. 4; pp. 784 - 792
• Main Authors: Ouchi, Yasuomi, Kanno, Toshihiko, Okada, Hiroyuki, Yoshikawa, Etsuji, Futatsubashi, Masami, Nobezawa, Shuji, Torizuka, Tatsuo, Tanaka, Keisei
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.04.2001; Oxford Publishing Limited (England)
• Subjects: [11C]CFT = 11C-labelled 2-β-carbomethoxy-3β-(4-fluorophenyl) tropane; ABP = arterial blood pressure; AC–PC = anterior–posterior intercommissural line; Aged; ANCOVA = analysis of covariance; ANOVA = analysis of variance; Arteries; BA = Brodmann area; Biological and medical sciences; Blood Pressure; Carbon Radioisotopes; Carrier Proteins - metabolism; Caudate Nucleus - diagnostic imaging; Caudate Nucleus - metabolism; Cocaine - analogs & derivatives; Cocaine - pharmacokinetics; Corpus Striatum - diagnostic imaging; Corpus Striatum - metabolism; DAT = dopamine transporter; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine - metabolism; dopamine availability; Dopamine Plasma Membrane Transport Proteins; Dopamine Uptake Inhibitors - pharmacokinetics; Female; Frontal Lobe - diagnostic imaging; Frontal Lobe - metabolism; FWHM = full width at half maximum; Gait; Gyrus Cinguli - diagnostic imaging; Gyrus Cinguli - metabolism; Heart Rate; Humans; Magnetic Resonance Imaging; Male; Medical sciences; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Neurology; Parkinson Disease - diagnostic imaging; Parkinson Disease - metabolism; Parkinson Disease - physiopathology; Parkinson's disease; PET; PR = pulse rate; Putamen - diagnostic imaging; Putamen - metabolism; RI = ratio index; ROI = region of interest; SPM = statistical parametric mapping; statistical parametric mapping; Substantia Nigra - diagnostic imaging; Substantia Nigra - metabolism; Tomography, Emission-Computed; UPDRS = Unified Parkinson's Disease Rating Scale; Walking; Radionuclide study; Human; Gait disorder; Nervous system diseases; Dopamine; Biological transport; Parkinson disease; Basal ganglion; Cerebral disorder; Walking; Central nervous system disease; Complication; Degenerative disease; Extrapyramidal syndrome; Positron; Emission tomography
• ISSN: 0006-8950; 1460-2156; 1460-2156
• DOI: 10.1093/brain/124.4.784

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-β-carbomethoxy-3β-(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.