OBJECTIVETo investigate the mRNA expression of dopamine receptor D2 (DRD2) and dopamine transporter (DAT) in peripheral blood lymphocytes before and after treatment in children with tic disorder (TD).

METHODSRT-PCR was used to measure the mRNA expression of DRD2 and DAT in peripheral blood lymphocytes before and after treatment in 60 children with TD. The correlations between mRNA expression of DRD2 and DAT and the severity of TD were analyzed. Sixty healthy children served as the control group.

RESULTSBefore treatment, the children with TD had a significant increase in the mRNA expression of DRD2 and DAT compared with the control group (P<0.05). After 3 months of treatment with oral aripiprazole, the mRNA expression of DRD2 decreased significantly (P<0.05), while that of DAT showed no significant changes in children with TD. In the children with moderate or severe TD, the mRNA expression of DRD2 was positively correlated with Yale Global Tic Severity Scale (YGTSS) score (P<0.05). In the children with moderate TD, the mRNA expression of DAT was positively correlated with YGTSS score (P<0.05).

CONCLUSIONSIn children with TD, the mRNA expression of DRD2 in peripheral blood lymphocytes can be used as one of the indicators for diagnosing TD, assessing the severity of TD, and evaluating clinical outcomes.

Adolescent ; Child ; Child, Preschool ; Dopamine Plasma Membrane Transport Proteins ; genetics ; Female ; Humans ; Lymphocytes ; metabolism ; Male ; RNA, Messenger ; blood ; Receptors, Dopamine D2 ; genetics ; Tic Disorders ; drug therapy ; metabolism ; mortality

Sporadic spastic paraplegia (SSP) and hereditary spastic paraplegia (HSP) belong to a clinical and genetically heterogeneous group of disorders characterized by progressive spasticity and weakness in the lower extremities. The symptoms are associated with pyramidal tract dysfunction and degeneration of the corticospinal tracts. Parkinsonism is uncommon in SSP/HSP patients. However, both disorders are associated with damage to the nigrostriatal dopaminergic system. In the present study, the clinical features of patients with SSP/HSP were investigated, and nigrostriatal dopaminergic binding potential was assessed using dopamine transporter (DAT) single-photon emission computer tomography (SPECT). Nine patients with spastic paraplegia participated in the present study. The subjects underwent DAT SPECT using the agent [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato (3-)-N2,N20,S2,S20]oxo-[IR-(exo-exo)])-[99mTc]technetium ([99mTc]TRODAT-1). The [99mTc]TRODAT-1 SPECT images of five patients appeared normal, whereas the images of four patients revealed reduced striatal ligand uptake. Among the four patients with reduced uptake, two had parkinsonism, and one exhibited periodic limb movements and restless leg syndrome. Our DAT SPECT imaging study shows that reduced DAT density may be observed in patients with parkinsonism. The results of the present study offer an explanation for the spectrum of spastic paraplegia symptoms and the progression of the disorder.
Adult ; Aged ; Brain/*radionuclide imaging ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Female ; Humans ; Male ; Middle Aged ; Organotechnetium Compounds/diagnostic use ; Paraplegia/diagnosis/genetics/*radionuclide imaging ; Parkinsonian Disorders/complications/genetics/*radionuclide imaging ; Pyramidal Tracts ; Radiopharmaceuticals/diagnostic use ; Spastic Paraplegia, Hereditary/diagnosis/genetics/*radionuclide imaging ; Tomography, Emission-Computed, Single-Photon

OBJECTIVETo assess the association of a 40 bp variable number of tandem repeat (VNTR) polymorphism within 3 untranslated region of dopamine transporter gene (DAT1) with Tourette syndrome (TS) in a Chinese Han population.

METHODSA total of 160 TS patients and their parents were recruited. The VNTR polymorphism was detected with polymerase chain reaction-VNTR analysis, and its association with TS and its subtypes were assessed through a family-based association study comprising transmission disequilibrium test (TDT) and haplotype relative risk (HRR) analysis.

RESULTSThe repeat numbers at the DAT1 40 bp locus were 11, 10, 9, 7.5 and 7 among the patients and their parents, with the most common type being a 10-repeat allele. No significant association was detected between the polymorphism and TS (TDT: X ² = 0.472, df = 1, P = 0.583; HRR: X ² = 0.313, P = 0.576, OR = 0.855, 95%CI: 0.493-1.481).

CONCLUSIONOur data suggested that the VNTR polymorphism of DAT1 gene is not associated with susceptibility to TS in Chinese Han population. However, our results are to be validated in larger sets of patients collected from other populations.

Adolescent ; Adult ; Asian Continental Ancestry Group ; ethnology ; genetics ; Child ; Child, Preschool ; Dopamine Plasma Membrane Transport Proteins ; genetics ; Female ; Humans ; Male ; Minisatellite Repeats ; Pedigree ; Polymorphism, Genetic ; Tourette Syndrome ; ethnology ; genetics ; Young Adult

OBJECTIVETo investigate the relationship between 5-HTTLPR and/or DRD4 gene polymorphisms and the accident tendentiousness of drivers.

METHODSA case-control study, including 42 patients and 46 controls, were performed using type-A behavior questionnaire and EPQ scale. 5-HTTLPR and DRD4 gene -521 C/T were detected by the PCR-RFLP technique.

RESULTSThe scores of type-A behavior questionnaires, such as TH and TH + CH in exposure group were significantly higher than those in control group (P < 0.05). P and N scores of EPQ questionnaires in exposure group were significantly higher than those in control group, and L score in exposure group was significantly lower than that in control group (P < 0.05 or P < 0.01). There were significant differences in the frequencies of the genotypes and alleles of 5-HTTLPR gene between the cases and the controls (P < 0.05), but there were no significant differences in the frequencies of the genotypes and alleles of DRD4 gene between the two groups (P > 0.05). In the drivers with the accident tendentiousness, P scores in the cases with homozygous genotypes of the S/S in 5-HTTLPR gene were significantly higher than those in the cases with the genotypes of S/L and L/L in 5-HTTLPR gene (P > 0.05). E scores in subjects with homozygous genotypes of the T/T in DRD4 gene were significantly higher than those in subjects with genotypes of the T/C+C/C in DRD4 gene (P > 0.05).

CONCLUSIONThe driver accident tendentiousness may be associated with 5-HTTLPR gene, but not associated with DRD4 gene. The two genes are associated with the type-A behavior and personality characteristics of drivers with accident tendentiousness. However, 5-HTTLPR and DRD4 gene may not have synergism in these behaviors and personality.

Accidents, Traffic ; statistics & numerical data ; Adult ; Automobile Driving ; Case-Control Studies ; Genotype ; Humans ; Male ; Personality ; genetics ; Polymorphism, Genetic ; Receptors, Dopamine D4 ; genetics ; Serotonin Plasma Membrane Transport Proteins ; genetics

OBJECTIVETo explore the correlations of dopamine transporter gene (DAT) and dopamine D(2) receptor gene (DRD2) to stuttering.

METHODSTo examine the correlations of the 5 single nucleotide polymorphisms (SNPs) in dopaminergic gene (C252T, C1804T, and C1820T in DAT gene, and T1054C and C1072T in DRD(2) gene) to stuttering in Han Chinese individuals, a case-control study involving 112 patients with stuttering and 112 gender-matched controls was carried out. Genotyping was performed by a combined approach using polymerase chain reaction (PCR) and pyrosequencing.

RESULTSC1804T showed no polymorphism in either the patients or the control subjects and was therefore excluded from the following analysis. The C allele frequency at C1072T site was significantly higher, but T allele frequency significantly lower in the stuttering group than in the control group. The patients had significantly higher CC and lower CT genotype frequencies than the control group. There were no significant differences in the allelic frequencies of C252T, C1820T and T1054C between the patients and the controls, suggesting a Hardy-Weinberg equilibrium at these 3 loci.

CONCLUSIONThe presence of the C allele at C1072T in DRD(2) gene is associated with increased susceptibility to stuttering in Han Chinese, whereas the T allele provides protection against the onset of stuttering.

Adult ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; China ; ethnology ; Dopamine Plasma Membrane Transport Proteins ; genetics ; Female ; Genotype ; Humans ; Male ; Polymorphism, Single Nucleotide ; Receptors, Dopamine D2 ; genetics ; Stuttering ; genetics ; Young Adult

BACKGROUNDParaquat (PQ; 1,1'-dimethyl-4,4'-bipyridinium), a widely used herbicide, has been repeatedly suggested as a potential etiologic factor for the development of Parkinson's disease (PD), owing to its structural similarity to the known dopaminergic neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This study aimed to observe the influence of paraquat on nigrostriatal dopaminergic neurons in C57BL/6 mice.

METHODSA total of 24 male C57BL/6 mice were assigned randomly to 3 groups: control group (treated by saline), PQ treated group, and MPTP treated group. Mice in PQ treated group were taken orally with PQ (10 mg/kg) daily for four months. Locomotor activity was measured. Level of dopamine (DA) and its metabolites levels in the striatum were measured by high-performance liquid chromatography with an electrochemical detector (HPLC-ECD), and tyrosine hydroxylase (TH) positive neurons were detected by using immunohistochemistry. At the same time, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and the content of malondialdehyde (MDA) in substantia nigra were measured by spectrophotometry. mRNA expression of dopamine transporter (DAT) in dopaminergic neurons of substantia nigra was also determined by reverse transcription (RT)-PCR technique.

RESULTSLocomotor activities were significantly impaired in the PQ treated group. Level of DA and its metabolites levels in the striatum were declined. The activities of SOD and GSH-PX were decreased, and the content of MDA was increased in PQ treated mice compared with that in control group. Numbers of TH positive neurons and the mRNA expression of DAT in substantia nigra of mice were also decreased after PQ taken orally for four months.

CONCLUSIONSThe present study suggests that chronic oral administration of PQ could trigger dopaminergic neuron degeneration. Oxidative stress could be involved in the pathogenic mechanism of PD induced by PQ.

Administration, Oral ; Animals ; Behavior, Animal ; drug effects ; Corpus Striatum ; drug effects ; Dopamine ; analysis ; metabolism ; Dopamine Plasma Membrane Transport Proteins ; analysis ; genetics ; Glutathione Peroxidase ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Paraquat ; toxicity ; Parkinson Disease ; etiology ; RNA, Messenger ; analysis ; Substantia Nigra ; drug effects ; Superoxide Dismutase ; metabolism

OBJECTIVETo explore the mechanism of electroacupuncture scalp point-through-point therapy in the treatment of Parkinson's disease.

METHODSThirty-six Wistar rats were randomly divided into a normal group, a sham-operation group, a model group and a point-through-point therapy group. 6-()HDA was injected into left striatum to made lateralization Parkinson's disease rat model. The point-through-point therapy group was treated with electroacupuncture at "Baihui" (GV 20 )-through-"Taiyang" (EX-NH 5), once each day, 6 days constituting one course, for 2 courses, and the rats of other groups were not treated. HE staining method was used for observation of the histo-morphologic changes of the substantia nigra neurons, and RT-PCR for the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNAs.

RESULTSThe expressions of TH mRNA (1.22 +/- 0. 19) and DAT mRNA (0.62-0.11) in the point-through-point therapy group were significantly higher than (0.65 +/- 0.17) and (0.41 +/- 0.08) in the model group, respectively (all P < 0.05). As compared with the model group, the number of neurons in the substantia nigra increased and degeneration of the neurons relieved in the point-through-point therapy group.

CONCLUSIONThe electroacupuncture scalp point-through-point therapy can increase expressions of TH mRNA and DAT mRNA in the substantia nigra in the Parkinson's disease model rat, and promote synthesis and reuptake of dopamine, hence Parkinson's disease is cured.

Acupuncture Points ; Animals ; Disease Models, Animal ; Dopamine Plasma Membrane Transport Proteins ; genetics ; metabolism ; Electroacupuncture ; Female ; Gene Expression ; Humans ; Male ; Parkinson Disease ; genetics ; metabolism ; therapy ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Substantia Nigra ; metabolism ; Tyrosine 3-Monooxygenase ; genetics ; metabolism

OBJECTIVETo investigate the inhibitory effect of antisense oligonucleotides (ODN) on dopamine transporter (DAT) in rats and observe the response of the rats to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

METHODSThe cannula was implanted in the substantia nigra compacta under a rat stereotaxic device, through which drugs were used. The rats with successful operation were divided randomly into four groups, and received injection of antisense, sense, missense oligonucleotides and saline respectively, in the substantia nigra compacta of each rat via the cannula, followed by MPTP (30 mg/kg) injection. Behavior of the rats was observed and immunohistochemistry was carried out to check the expression of DAT and apoptosis of dopamine cell.

RESULTSThe expression of DAT (positive unit, PU) in the substantia nigra compacta in rats was 6.65+/- 1.67 in the antisense ODN group, 12.41+/- 2.46 in saline group, 11.45+/- 1.17 in sense ODN group, and 10.35+/- 2.89 in missense ODN group. The expression of DAT was lower in the antisense ODN group than that of the other three groups (P< 0.01). The rotation of the rats induced by apomorphine was slower than that of the other three groups(P< 0.05). The apoptotic cells (21.4+/- 5.6) in the antisense ODN group (200x ) were less than that of the other three groups (61.6+/- 19.7, 56.5+/- 16.3, 52.2+/- 12.5 respectively), (P< 0.01).

CONCLUSIONThe expression of DAT can be inhibited effectively by the antisense ODN, and the response of the rats to the MPTP was reduced upon DAT inhibition.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; pharmacology ; Animals ; Apomorphine ; pharmacology ; Dopamine Plasma Membrane Transport Proteins ; genetics ; physiology ; Immunohistochemistry ; Male ; Oligonucleotides, Antisense ; genetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the expression of dopamine D2 receptors (D2R) and dopamine transportors (DAT) located in the medial prefrontal contex (mPFC) in high and low conditioned place preference (CPP) rats, and to unveil the possible mechanism leading to different CPP susceptibilities. METHODS: One hundred and sixty male Sprague-Dawley rats were randomly assigned into an experiment group (n = 130) and a control group (n = 30). The experiment group was re-classified into 2 groups according to CPP values:high preference group (HP group) and low preference group (LP group). According to the execution time-points after the last administration, the HP and LP group was classified into a 3-hour group (3 h), a 72-hour group (J3d), and a 14-day group (J14d), respectively. At 3 hours, 72 hours, and 14 days after the final injection, rats were killed and cardio-perfused, and the brains were removed and sliced up coronarily. The mRNA levels of D2R and DAT in mPFC were determined with in situ hybridization. RESULTS: There were no significant differences of pretest scores staying at the non-preference chamber among the groups(P = 0.470). However, the test scores of the CPP time stayed at pretest natural preference in the HP group were significantly higher than those of the LP group(P = 0.000). In 3h, J3d, and J14d groups,the expressions of D2R mRNA in the HP group (125.43 +/- 2.90 approximately 142.92 +/- 3.32) were lower than those of LP group (122.25 +/- 2.20 approximately 136.67 +/-5.39) (P = 0.000). In 3h and J3d,the expressions of DAT mRNA in the HP group (157.00 +/- 3.55 approximately 145.15 +/- 3.69) were significantly lower than those of the LP group (150.69 +/- 3.12 approximately 138.84 +/- 3.99) (P = 0.000). In J14d, there were no differences among 3 groups in mPFC (P = 0.458). CONCLUSION D2R and DAT may be correlated closely and underlie the different susceptibilities to morphine induced CPP.
Animals ; Conditioning, Psychological ; drug effects ; Disease Susceptibility ; metabolism ; Dopamine Plasma Membrane Transport Proteins ; biosynthesis ; genetics ; Male ; Morphine Dependence ; metabolism ; Prefrontal Cortex ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine D2 ; biosynthesis ; genetics

Human personality traits have a considerable genetic component. Cloninger et al. were the first to postulate that certain personality traits, such as novelty seeking, are related to the dopamine neurotransmitter system. In this study, we investigated the associations between dopamine receptor D4 (DRD4) exon III and dopamine transporter (DAT1) polymorphisms and personality traits. The DRD4 and DAT1 gene polymorphisms were genotyped in 214 healthy Korean subjects, whose personality traits were assessed with the Temperament and Character Inventory (TCI). There were no significant differences between scores of TCI temperament dimensions (novelty seeking, harm avoidance, reward dependence, and persistence) and DRD4 gene polymorphism. The DAT1 gene polymorphisms also showed no significant association with any of the temperament subscales of the TCI. These data suggest that DRD4 and DAT1 gene polymorphism may not associated with personality traits in a Korean population.
Temperament ; Receptors, Dopamine D4/*genetics ; *Polymorphism, Genetic ; Personality/*genetics ; Male ; Korea ; Humans ; Female ; Dopamine Plasma Membrane Transport Proteins/*genetics ; Adult