33 research outputs found
Subregional 6-[18F]fluoro-Ęź-m-tyrosine Uptake in the Striatum in Parkinson's Disease
<p>Abstract</p> <p>Background</p> <p>In idiopathic Parkinson's disease (PD) the clinical features are heterogeneous and include different predominant symptoms. The aim of the present study was to determine the relationship between subregional aromatic l-amino acid decarboxylase (AADC) activity in the striatum and the cardinal motor symptoms of PD using high-resolution positron emission tomography (PET) with an AADC tracer, 6-[<sup>18</sup>F]fluoro-Ęź-<it>m</it>-tyrosine (FMT).</p> <p>Methods</p> <p>We assessed 101 patients with PD and 19 healthy volunteers. PD was diagnosed based on the UK Brain Bank criteria by two experts on movement disorders. Motor symptoms were measured with the Unified Parkinson's Disease Rating Scale (UPDRS). FMT uptake in the subregions of the striatum was analyzed using semi-automated software for region-of-interest demarcation on co-registered magnetic resonance images.</p> <p>Results</p> <p>In all PD patients, FMT uptake was decreased in the posterior putamen regardless of predominant motor symptoms and disease duration. Smaller uptake values were found in the putamen contralateral to the side with more affected limbs. The severity of bradykinesia, rigidity, and axial symptoms was correlated with the decrease of FMT uptake in the putamen, particularly in the anterior part. No significant correlation was observed between tremors and FMT uptake.</p> <p>Conclusions</p> <p>Decrease of FMT uptake in the posterior putamen appears to be most sensitive in mild PD and uptake in the anterior putamen may reflect the severity of main motor symptoms, except for tremor.</p
No Differential Regulation of Dopamine Transporter (DAT) and Vesicular Monoamine Transporter 2 (VMAT2) Binding in a Primate Model of Parkinson Disease
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 (rs = 0.83, rs = 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
In vivo quantification of glial activation in minipigs overexpressing human α-synuclein
Nigrostriatal proteasome inhibition impairs dopamine neurotransmission and motor function in minipigs
Electroconvulsive Therapy Alters Dopamine Signaling in the Striatum of Non-human Primates
Electroconvulsive therapy (ECT) is one of the most effective therapies for depression and has beneficial motor effects in parkinsonian patients. However, little is known about the mechanisms of therapeutic action of ECT for either condition. The aim of this work was to explore the impact of ECT on dopaminergic function in the striatum of non-human primates. Rhesus monkeys underwent a course of six ECT treatments under a human clinical protocol. Longitudinal effects on the dopaminergic nigrostriatal system were studied over 6 weeks using the in vivo capabilities of positron emission tomography (PET). PET scans were performed prior to the onset of ECT treatments and at 24–48 h, 8–10 days, and 6 weeks after the final ECT treatment. Early increases in dopamine transporter and vesicular monoamine transporter 2 binding returned to baseline levels by 6 weeks post-ECT. Transient increases in D1 receptor binding were also observed, whereas the binding potential to D2 receptors was unaltered. The increase in dopaminergic neurotransmission suggested by our results may account in part for the therapeutic effect of ECT in mood disorders and Parkinson's disease