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Dopaminergic Function (dopaminergic + function)
Kinds of Dopaminergic Function Selected AbstractsSubstantial Thalamostriatal Dopaminergic Defect in Unverricht-Lundborg DiseaseEPILEPSIA, Issue 9 2007Miikka Korja Summary:,Purpose: Unverricht-Lundborg disease (ULD) is currently classified as progressive myoclonus epilepsy. Myoclonus, the characteristic symptom in ULD, suggests that dopamine neurotransmission may be involved in the pathophysiology of ULD. Our purpose was to examine brain dopaminergic function in ULD patients. Methods: Four genetically and clinically diagnosed ULD patients and eight healthy controls were scanned with [11C]raclopride-PET. PET images were coregistered to individual 1.5T MR images and region-of-interest analysis was performed for the striatum and thalamus. Standardized uptake values and individual voxel-wise binding potential maps of the patients and controls were also analyzed. Results: ULD patients had markedly higher (31,54%) dopamine D2-like receptor availabilities than healthy controls in both the striatum and the thalamus. The proportionally highest binding potentials were detected in the thalamus. There were no significant differences in the cerebellar uptake of [11C]raclopride in ULD patients versus healthy controls. Voxel-based results were in accordance with the region-of-interest analysis. Conclusions: These results suggest that dopaminergic modulation at the level of the striatum and thalamus could be a crucial factor contributing to the symptoms of ULD. In the light of our data, we propose that ULD with dopamine dysfunction and dyskinetic symptoms shares certain pathophysiological mechanisms with classical movement disorders. Future studies are therefore warranted to study the effect of dopaminergic pharmacotherapy in ULD. [source] Impaired water maze learning performance without altered dopaminergic function in mice heterozygous for the GDNF mutationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2001R. Gerlai Abstract Exogenous glial cell line-derived neurotrophic factor (GDNF) exhibits potent survival-promoting effects on dopaminergic neurons of the nigrostriatal pathway that is implicated in Parkinson's disease and also protects neurons in forebrain ischemia of animal models. However, a role for endogenous GDNF in brain function has not been established. Although mice homozygous for a targeted deletion of the GDNF gene have been generated, these mice die within hours of birth because of deficits in kidney morphogenesis, and, thus, the effect of the absence of GDNF on brain function could not be studied. Herein, we sought to determine whether adult mice, heterozygous for a GDNF mutation on two different genetic backgrounds, demonstrate alterations in the nigrostriatal dopaminergic system or in cognitive function. While both neurochemical and behavioural measures suggested that reduction of GDNF gene expression in the mutant mice does not alter the nigrostriatal dopaminergic system, it led to a significant and selective impairment of performance in the spatial version of the Morris water maze. A standard panel of blood chemistry tests and basic pathological analyses did not reveal alterations in the mutants that could account for the observed performance deficit. These results suggest that endogenous GDNF may not be critical for the development and functioning of the nigrostriatal dopaminergic system but it plays an important role in cognitive abilities. [source] Trifluoromethanesulfonic acid, an alternative solvent medium for the direct electrophilic fluorination of DOPA: new syntheses of 6-[18F]fluoro- L -DOPA and 6-[18F]fluoro- D -DOPAJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 14 2007Babak Behnam Azad Abstract Previous work from this laboratory has shown that the direct fluorination of 3, 4-dihydroxy-phenyl- L -alanine (L -DOPA) in anhydrous HF (aHF) or BF3/HF with F2 is an efficient method for the synthesis of 6-fluoro- L -DOPA. Since then, 18F-labeled 6-fluoro- L -DOPA ([18F]6-fluoro- L -DOPA) has been used to study presynaptic dopaminergic function in the human brain and to monitor gastrointestinal carcinoid tumors. This work demonstrates that the reactivity and selectivity of F2 toward L -DOPA in CF3SO3H is comparable with that in aHF. This new synthetic procedure has led to the production of [18F]fluoro- L -DOPA and [18F]fluoro-D-DOPA isomers in 17±2% radiochemical yields (decay corrected with respect to [18F]F2). The 2- and 6-FDOPA isomers were separated by HPLC and subsequently characterized by 19F NMR spectroscopy. The corresponding [18F]-FDOPA enantiomers have been obtained in clinically useful quantities by a synthetic approach that avoids the use of aHF. Copyright © 2007 John Wiley & Sons, Ltd. [source] Cyclin-dependent kinase 5 in synaptic plasticity, learning and memoryJOURNAL OF NEUROCHEMISTRY, Issue 2 2006Marco Angelo Abstract Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase with a multitude of functions. Although Cdk5 is widely expressed, it has been studied most extensively in neurons. Since its initial characterization, the fundamental contribution of Cdk5 to an impressive range of neuronal processes has become clear. These phenomena include neural development, dopaminergic function and neurodegeneration. Data from different fields have recently converged to provide evidence for the participation of Cdk5 in synaptic plasticity, learning and memory. In this review, we consider recent data implicating Cdk5 in molecular and cellular mechanisms underlying synaptic plasticity. We relate these findings to its emerging role in learning and memory. Particular attention is paid to the activation of Cdk5 by p25, which enhances hippocampal synaptic plasticity and memory, and suggests formation of p25 as a physiological process regulating synaptic plasticity and memory. [source] Neuroradiologic Evidence of Pre-Synaptic and Post-Synaptic Nigrostriatal Dopaminergic Dysfunction in Idiopathic Basal Ganglia Calcification: A Case ReportJOURNAL OF NEUROIMAGING, Issue 2 2010Takahiro Saito MD ABSTRACT Idiopathic basal ganglia calcification (IBGC) is a neuropathological condition known to manifest as motor disturbance, cognitive impairment, and psychiatric symptoms. The pathophysiology of the psychiatric symptoms of IBGC, however, remains controversial. A previous biochemical study suggested that dopaminergic impairment is involved in IBGC. We thus hypothesized that dopaminergic dysfunction might be related with the psychiatric manifestations of IBGC. We used positron emission tomography to measure glucose metabolism and dopaminergic function in the basal ganglia of an IBGC patient with psychiatric symptoms. The results showed that widespread hypometabolism was evident in the frontal, temporal, and parietal cortices while the decline in dopaminergic function was severe in the bilateral striatum. The functional decline of the dopamine system in the calcified area of the bilateral striatum and the disruption of cortico-subcortical circuits may contribute to clinical manifestations of IBGC in our patient. [source] Nigrostriatal dysfunction in homozygous and heterozygous parkin gene carriers: An 18F-dopa PET progression study,MOVEMENT DISORDERS, Issue 15 2009Nicola Pavese MD Abstract Little is known about the rate of progression of striatal dysfunction in subjects with parkin -linked parkinsonism. Being a heterozygous parkin gene carrier may confer susceptibility to Parkinson's disease (PD). In a previous 18F-dopa PET study, we reported that 69% of carriers of a single parkin mutation showed subclinical loss of putamen dopaminergic function. Using serial 18F-dopa PET, the present longitudinal study addresses rates of progression of nigrostriatal dysfunction in both compound heterozygous (parkin -linked parkinsonism) and single heterozygous parkin gene carriers. Three symptomatic patients who were compound heterozygotes for parkin gene mutations and six asymptomatic heterozygous carriers were clinically assessed and had 18F-dopa PET at baseline and again after 5 years. The patients with symptomatic parkin showed a mean 0.5% annual reduction in putamen 18F-dopa uptake over 5 years while caudate 18F-dopa uptake declined by a mean annual rate of 2 %. The asymptomatic heterozygote gene carriers showed a mean 0.56% annual reduction in putamen and 0.62 % annual reduction in caudate 18F-dopa uptake. Neurological examination at both baseline and follow-up showed no evidence of parkinsonism. Loss of nigrostriatal dysfunction in parkin -linked parkinsonism occurs at a very slow rate compared to the 9,12% annual loss of putamen 18F-dopa uptake reported for idiopathic PD. Although subclinical reductions of striatal 18F-dopa uptake are common in carriers of a single parkin mutation their slow rate of progression suggests that few if any of these will develop clinical parkinsonism. © 2009 Movement Disorder Society [source] Functional brain imaging in pure akinesia with gait freezing: [18F] FDG PET and [18F] FP-CIT PET analyses,MOVEMENT DISORDERS, Issue 2 2009Hee K. Park MD Abstract Pure akinesia with gait freezing (PAGF) has characteristic features, including freezing of gait and prominent speech disturbance without rigidity or tremor. The purpose of this study was to investigate changes in brain glucose metabolism and presynaptic dopaminergic function in PAGF. By using [18F] fluorodeoxyglucose (FDG) PET, 11 patients with PAGF were compared with 14 patients with probable progressive supranuclear palsy (PSP), 13 patients with Parkinson's disease (PD), and 11 normal controls. [18F] N -(3-fluoropropyl)-2,-carbon ethoxy-3,-(4-iodophenyl) nortropane (FP-CIT) PET was performed in 11 patients with PAGF and with 10 normal controls. The PAGF patients showed decreased glucose metabolism in the midbrain when compared with normal controls. PSP patients showed a similar topographic distribution of glucose hypometabolism with additional areas, including the frontal cortex, when compared with normal controls. The FP-CIT PET findings in patients with PAGF revealed severely decreased uptake bilaterally in the basal ganglia. These findings suggest that both PAGF and PSP may be part of the same pathophysiologic spectrum of disease. However, the reason why PAGF manifests clinically in a different manner needs to be further elucidated. © 2008 Movement Disorder Society [source] [123I] FP-CIT spect study in vascular parkinsonism and Parkinson's diseaseMOVEMENT DISORDERS, Issue 9 2007Jan Zijlmans MD Abstract There is substantial evidence to support a role for small vessel disease (SVD) as a cause for vascular parkinsonism (VP). Using [123I] FP-CIT SPECT (single photon emission computed tomography), we have tried to determine whether VP patients have pre-synaptic dopaminergic function similar to PD patients, and whether the severity of parkinsonian symptoms as well as the levodopa response in VP patients are correlated with pre-synaptic dopaminergic dysfunction. Thirteen patients fulfilling operational clinical criteria for VP had [123I] FP-CIT scans. Mean [123I] FP-CIT uptake in the basal ganglia was significantly lower in VP patients than in healthy controls, and the asymmetry index was not significantly different between these groups. In contrast, compared with the PD group, only the mean asymmetry index was significantly lower in VP patients. None of the parameters measured was significantly different between VP patients who had an insidious onset of parkinsonism (VPi) and those who had an acute onset (VPa). There was a significant correlation between the bilateral basal ganglia FP-CIT uptake reduction in the VP patients and UPDRS motor scores, but not with the mean % reduction in motor UPDRS after levodopa. We suggest that in the majority of VP patients, pre-synaptic dopaminergic function is reduced. The presence of a rather symmetrical FP-CIT uptake in the basal ganglia may help to distinguish VP from PD and could therefore be used as a criterion for the clinical diagnosis of VP. © 2007 Movement Disorder Society [source] Dopamine transporter: Basic aspects and neuroimagingMOVEMENT DISORDERS, Issue S7 2003Paola P. Piccini MD Abstract The plasma membrane dopamine transporter (DAT) is found exclusively in dopamine neurones and seems to be the defining molecule of the dopamine neurone. It provides effective control over the intensity of dopamine-mediated signalling by recapturing the neurotransmitter released by presynaptic neurones. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) represent unique techniques for assessing in vivo DAT distribution in humans and offer reliable methods for studying nigrostriatal dopaminergic function in health and disease. The characteristics of different DAT radiotracers, the modifying influences of factors such as age, gender, smoking habit, and dopaminergic drugs on DAT transporters as well as their implication in evaluation of neuroimaging studies are discussed. © 2003 Movement Disorder Society [source] Extrastriatal dopaminergic dysfunction in tourette syndromeANNALS OF NEUROLOGY, Issue 2 2010Thomas D. L. Steeves MD Objective Tourette syndrome (TS) is a neuropsychiatric disorder presenting with tics and a constellation of nonmotor symptoms that includes attention deficit hyperactivity disorder, obsessive,compulsive disorder, and impulse control disorders. Accumulated evidence from pharmacological trials and postmortem analyses suggests that abnormalities of dopaminergic neurotransmission play a key role in the pathogenesis of TS. A substantial body of evidence has also accrued to implicate regions outside the striatum in the generation of tics. Methods We initiated an [11C]FLB 457 positron emission tomography study in conjunction with an amphetamine challenge to evaluate extrastriatal dopamine (DA) D2/D3 receptor binding and DA release in a group of treatment-naive, adult TS patients compared with a group of age- and sex-matched controls. Results At baseline, TS patients showed decreased [11C]FLB 457 binding potentials bilaterally in cortical and subcortical regions outside the striatum, including the cingulate gyrus, middle and superior temporal gyrus, occipital cortex, insula, and thalamus. Amphetamine challenge induced DA release in both control and TS subjects bilaterally in many cortical regions; however, in TS patients, regions of increased DA release were significantly more widespread and extended more anteriorly to involve anterior cingulate and medial frontal gyri. Conversely, and in contrast to healthy controls, no significant DA release was noted in the thalami of TS patients. Interpretation These abnormalities of dopaminergic function localize to brain regions previously implicated in TS and suggest a mechanism for the hyperexcitability of thalamocortical circuits that has been documented in the disorder. ANN NEUROL 2010;67:170,181 [source] Cerebrospinal fluid metabolite and nigrostriatal dopaminergic function in Parkinson's diseaseACTA NEUROLOGICA SCANDINAVICA, Issue 1 2010K. Ishibashi Ishibashi K, Kanemaru K, Saito Y, Murayama S, Oda K, Ishiwata K, Mizusawa H, Ishii K. Cerebrospinal fluid metabolite and nigrostriatal dopaminergic function in Parkinson's disease. Acta Neurol Scand: 2010: 122: 46,51. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives,,, To evaluate the association between cerebrospinal fluid (CSF) homovanillic acid (HVA) concentrations and nigrostriatal dopaminergic function assessed by positron emission tomography (PET) imaging with carbon-11-labeled 2,-carbomethoxy-3,-(4-fluorophenyl)-tropane (11C-CFT), which can measure the dopamine transporter (DAT) density, in Parkinson's disease (PD). Methods,,,11C-CFT PET scans and CSF examinations were performed on 21 patients with PD, and six patients with non-parkinsonian syndromes (NPS) as a control group. Results,,, In the PD group, CSF HVA concentrations were significantly correlated with the striatal uptake of 11C-CFT (r = 0.76, P < 0.01). However, in the NPS group, two indices were within the normal range. Conclusions,,, In PD, CSF HVA concentrations correlate with nigrostriatal dopaminergic function. Therefore, CSF HVA concentrations may be an additional surrogate marker for estimating the remaining nigrostriatal dopaminergic function in case that DAT imaging is unavailable. [source] Critical role of Nitric Oxide on Nicotine-Induced Hyperactivation of Dopaminergic Nigrostriatal System: Electrophysiological and Neurochemical evidence in RatsCNS: NEUROSCIENCE AND THERAPEUTICS, Issue 3 2010Vincenzo Di Matteo Nicotine, the main psychoactive ingredient in tobacco, stimulates dopamine (DA) function, increasing DA neuronal activity and DA release. DA is involved in both motor control and in the rewarding and reinforcing effects of nicotine; however, the complete understanding of its molecular mechanisms is yet to be attained. Substantial evidence indicates that the reinforcing properties of drugs of abuse, including nicotine, can be affected by the nitric oxide (NO) system, which may act by modulating central dopaminergic function. In this study, using single cell recordings in vivo coupled with microiontophoresis and microdialysis in freely moving animals, the role of NO signaling on the hyperactivation elicited by nicotine of the nigrostriatal system was investigated in rats. Nicotine induced a dose-dependent increase of the firing activity of the substantia nigra pars compacta (SNc) DA neurons and DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release in the striatum. Pharmacological manipulation of the NO system did not produce any change under basal condition in terms of neuronal discharge and DA release. In contrast, pretreatments with two NO synthase (NOS) inhibitors, N-,-nitro- l -arginine methyl ester (l -NAME) and 7-nitroindazole (7-NI) were both capable of blocking the nicotine-induced increase of SNc DA neuron activity and DA striatal levels. The effects of nicotine in l -NAME and 7-NI-pretreated rats were partially restored when rats were pretreated with the NO donor molsidomine. These results further support the evidence of an important role played by NO on modulation of dopaminergic function and drug addiction, thus revealing new pharmacological possibilities in the treatment of nicotine dependence and other DA dysfunctions. [source] | |||||||||||||