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ABSTRACT: ObjectiveClinical evidence indicates that the Tourette’s syndrome (TS) is associated with hyperactivity of the dopaminergic system;
however, imaging studies of dopamine transporter (DAT) in TS patients remain controversial. In this study, we aimed to study
DAT binding capacities in a relatively larger sample of drug-naive patients with TS in comparison with controlled subjects
by 99mTc-TRODAT-1 SPECT/CT imaging. We also aimed to look for any possible correlations between DAT and age, disease duration or
tic severity of TS, which have not been thoroughly investigated in previous studies. We tried to provide more evidence for
the understanding of the physiopathological mechanism of TS from the molecular imaging perspective.
MethodsEighteen drug-naive patients with TS and 8 age- and gender-matched healthy subjects were recruited. Severity of TS was measured
with Yale Global Tic Severity Scale. Brain SPECT/CT was performed 2.5h after injection of 99mTc-TRODAT-1. Regions of interest were drawn on the striatum including its sub-regions of caudate and putamen. The cerebellum
was used as the reference region. DAT uptake ratio was calculated by subtracting the mean counts per pixel in the cerebellum
from the mean counts per pixel in the striatum, caudate or putamen and by dividing the result by the mean counts per pixel
in the cerebellum. Comparisons of DAT uptake ratios between TS patients and controls, and comparisons in bilateral striatum
and sub-regions in TS patients were carried out. Correlation analysis between DAT uptake ratios and clinical data were also
conducted.
ResultsTS patients showed significantly higher uptake of 99mTc-TRODAT-1 in bilateral striatum in comparison with the controls. There was no group-specific preferential lateralization
in striatal uptake. DAT uptake ratios were not correlated with age and tic severity scores, but significant negative correlation
with disease duration was found.
ConclusionsHigh level of DAT was demonstrated in drug-naive TS patients compared with normal controls, and it was negatively correlated
with TS duration. Therefore, with the extension of the disease duration, certain degree of adaptation might occur in TS patients
to compensate for the DAT increase, which suggested that hyper-functional DAT might be involved in the early pathophysiological
changes of TS.
KeywordsDopamine transporter (DAT)-
99mTc-TRODAT-1-Tourette’s syndrome (TS)-SPECT/CT
Annals of Nuclear Medicine 04/2012; 24(7):515-521. · 1.50 Impact Factor
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ABSTRACT: The key pathological feature of Parkinson's disease (PD) is selective degeneration of the neuromelanin (NM)-pigmented dopaminergic neurons in the substantia nigra (SN). NM, like other risk factors, such as oxidative stress (OS) and α-synuclein (α-syn), is involved in the pathogenesis of PD. But whether or not NM synergizes with α-syn or OS in the pathogenesis of PD remains unexplored. In the present study, we examined the effects of NM on cellular viability, apoptosis and free radical production in α-syn over-expressing human neuroblastoma cell line (SK-N-SH) in the presence or absence of the oxidizer Fenton's Reagent (FR). We showed that NM synergized with FR in suppressing cell viability, and in inducing apoptosis and hydroxyl radical production in all SK-N-SH cell lines. α-Syn over-expressing cells exhibited more pronounced effect, especially the A53T mutation. Our findings suggest that NM synergizes with both OS and α-syn in conferring dopaminergic vulnerability, adding to our understanding of the pathogenesis of PD.
Acta Neurovegetativa 12/2011; 119(6):685-91. · 2.73 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Clinical evidence indicates that the Tourette's syndrome (TS) is associated with hyperactivity of the dopaminergic system; however, imaging studies of dopamine transporter (DAT) in TS patients remain controversial. In this study, we aimed to study DAT binding capacities in a relatively larger sample of drug-naive patients with TS in comparison with controlled subjects by (99m)Tc-TRODAT-1 SPECT/CT imaging. We also aimed to look for any possible correlations between DAT and age, disease duration or tic severity of TS, which have not been thoroughly investigated in previous studies. We tried to provide more evidence for the understanding of the physiopathological mechanism of TS from the molecular imaging perspective.
Eighteen drug-naive patients with TS and 8 age- and gender-matched healthy subjects were recruited. Severity of TS was measured with Yale Global Tic Severity Scale. Brain SPECT/CT was performed 2.5 h after injection of (99m)Tc-TRODAT-1. Regions of interest were drawn on the striatum including its sub-regions of caudate and putamen. The cerebellum was used as the reference region. DAT uptake ratio was calculated by subtracting the mean counts per pixel in the cerebellum from the mean counts per pixel in the striatum, caudate or putamen and by dividing the result by the mean counts per pixel in the cerebellum. Comparisons of DAT uptake ratios between TS patients and controls, and comparisons in bilateral striatum and sub-regions in TS patients were carried out. Correlation analysis between DAT uptake ratios and clinical data were also conducted.
TS patients showed significantly higher uptake of (99m)Tc-TRODAT-1 in bilateral striatum in comparison with the controls. There was no group-specific preferential lateralization in striatal uptake. DAT uptake ratios were not correlated with age and tic severity scores, but significant negative correlation with disease duration was found.
High level of DAT was demonstrated in drug-naive TS patients compared with normal controls, and it was negatively correlated with TS duration. Therefore, with the extension of the disease duration, certain degree of adaptation might occur in TS patients to compensate for the DAT increase, which suggested that hyper-functional DAT might be involved in the early pathophysiological changes of TS.
Annals of Nuclear Medicine 08/2010; 24(7):515-21. · 1.50 Impact Factor
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ABSTRACT: To study the association of two polymorphisms of ubiquitin carboxy-terminal hydrolase-L1 gene(UCH-L1), the 54C/A in exon 3 and the 277C/G in exon 4, with sporadic Parkinson's disease(PD) in Hans from North China.
Polymerase chain reaction-restriction fragment length polymorphism was used to investigate the genotype and allele frequencies of the UCH-L1 C/A and C/G loci, in a case-control study including 75 sporadic PD and 100 randomly selected healthy control subjects.
(1)There was significant difference between PD patients and controls in the frequencies of UCH-L1 genotype and C/A allele(P<0.05). The frequencies of allele A and genotype AA were both significantly lower in PD patients than that in the controls(P<0.05).(2)There was no polymorphism in the UCH-L1 C/G locus in all cases and controls.
(1)There might be association between the polymorphisms of UCH-L1 C/A locus and sporadic PD in Han population from North China.(2)There is no polymorphism in the UCH-L1 C/G locus in Hans from this region.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 10/2008; 25(5):586-7.
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Human Genetics 04/2004; 114(4):403. · 5.07 Impact Factor
