Dopamine receptor and dopamine transporter in obesity: A meta-analysis.

The brain plays a major role in controlling the desire to eat. This meta-analysis aimed to assess the association between dopamine receptor (DR) availability and dopamine transporter (DAT) availability, measured using positron emission tomography, and obesity. We performed a systematic search of MEDLINE (from inception to November 2020) and EMBASE (from inception to November 2020) for articles published in English using the keywords "dopamine receptor," "dopamine transporter," "obesity," and "neuroimaging." Body mass index (BMI) and the corresponding binding potential (BPND ) were extracted from figures in each study using Engauge Digitizer, version 12.1, and plotted for radiopharmaceuticals and regions of interest (ROIs). Five studies involving 119 subjects with DR and five studies including 421 subjects with DAT were eligible for inclusion in this study. In overweight or obese subjects with BMI of 25 kg/m2 or higher, DR availability from 11 C-Racloprie was negatively associated with BMI. However, DR availability from 11 C-PHNO was positively associated with BMI. DAT ratio was calculated after dividing DAT availabilities of overweight/obese BMI with mean DAT availabilities of normal BMI. The association between DAT ratio and BMI was not significant regardless of radiopharmaceuticals. In conclusion, dopamine plays a main role in the reward system with regard to obesity. Overweight and obese subjects had negative association between DR availability from 11 C-Raclopride and BMI. However, the association of DR availability with BMI was dependent on radiopharmaceuticals. DAT availability did not show the significant relationship with BMI regardless of radiopharmaceuticals.

Characterization of the nigroestriatal system in a sample of patients with amyotrophic lateral sclerosis / Caracterização do sistema nigroestriatal em uma amostra de pacientes com esclerose lateral amiotrófica

Abstract Background The coexistence of amyotrophic lateral sclerosis (ALS) with clinical forms of Parkinson disease (PD), although uncommon, is found to a greater degree than one would expect by chance. The pathological mechanisms of ALS and PD are still not fully understood, and the coexistence of these two diseases suggests that they could share mechanisms in common. Objective Here we present a sample of patients with clinically definitive or probable ALS who were evaluated with single-photon emission computed tomography SPECT/TRODAT and compared with non-ALS controls. Methods Patients with clinically definite or probable ALS were assessed with the amyotrophic lateral sclerosis functional rating scale (ALSFRS) to define severity and had their demographic data collected. The TRODAT results of patients with ALS were compared with those of patients with a diagnosis of PD with less than 10 years of duration, and with patients with a diagnosis of others movement disorders not associated with neurodegenerative diseases. Results A total of 75% of patients with ALS had TRODAT results below the levels considered normal; that was also true for 25% of the patients in the control group without neurodegenerative disease, and for 100% of the patients in the PD group. A statistically significant difference was found between patients with ALS and the control group without neurodegenerative disease in the TRODAT values < 0.05. Conclusions Our study fits with the neuropathological and functional evidence that demonstrates the existence of nigrostriatal dysfunction in patients with ALS. Further research to better understand the role of these changes in the pathophysiological process of ALS needs to be performed.

Resumo Antecedentes A coexistência da esclerose lateral amiotrófica (ELA) com formas clínicas da doença de Parkinson (DP), embora incomum, é encontrada em um grau maior do que seria esperado ao acaso. Os mecanismos patológicos da ELA e da DP ainda não são totalmente compreendidos e a coexistência dessas duas doenças sugere que elas podem compartilhar mecanismos em comum. Objetivo Apresentamos uma amostra de pacientes com ELA clinicamente definida ou provável que foram avaliados com tomografia computadorizada por emissão de fóton único (SPECT)/TRODAT e comparados com controles sem ELA. Métodos Pacientes com ELA clinicamente definida ou provável foram avaliados com a escala funcional de esclerose lateral amiotrófica (ALSFRS) para definir a gravidade e foram coletados os seus dados demográficos. Os resultados do TRODAT de pacientes com ELA foram comparados com aqueles de pacientes com diagnóstico de DP com menos de 10 anos de duração e com pacientes com diagnóstico de outros distúrbios do movimento não associados a doenças neurodegenerativas. Resultados Um total de 75% dos pacientes com ELA apresentou resultados de TRODAT abaixo dos níveis considerados normais; 25% no grupo controle sem doença neurodegenerativa e 100% no grupo DP. Uma diferença estatisticamente significativa foi encontrada entre os pacientes com ELA e o grupo controle sem doença neurodegenerativa nos valores de TRODAT p< 0,05. Conclusões Nosso estudo está de acordo com as evidências neuropatológicas e funcionais que demonstram a existência de disfunção nigroestriatal em pacientes com ELA. Mais pesquisas para entender melhor o papel dessas mudanças no processo fisiopatológico da ELA precisam ser realizadas.

Limited power of dopamine transporter mRNA mapping for predicting dopamine transporter availability.

Dopamine transporters (DAT) are transmembrane proteins that translocate dopamine from the extracellular space into presynaptic neurons. We aimed to investigate the predictive power of DAT mRNA for DAT protein expression, measured using positron emission tomography (PET). We performed 18 F-FP-CIT PET scans in 35 healthy individuals. Binding potentials (BPND ) from the ventral striatum, caudate nucleus, putamen, and middle frontal, orbitofrontal, cingulate, parietal, and temporal cortices were measured. DAT gene expression data were obtained from the freely available Allen Human Brain Atlas derived from six healthy donors. The auto-correlation of PET-derived BPND s for DAT was intermediate (mean ρ2  = .66) with ρ2 ranging from .0811 to 1. However, the auto-correlation of mRNA expression was weak across the probes with a mean ρ2 of .09-.23. Cross-correlations between PET-derived BPND s and mRNA expression were weak with a mean ρ2 ranging from 0 to .22 across the probes. In conclusion, we observed weak associations between DAT mRNA expression and DAT availability in human brains. Therefore, DAT mRNA mapping may have only limited predictive power for DAT availability in humans. However, the difference in distribution of DAT mRNA and DAT protein may influence this limitation.

SLC6A3 gene polymorphisms are associated with striatal dopamine transporter changes after glucose loading.

We investigated the association between SLC6A3 gene polymorphisms and changes in dopamine transporter (DAT) availability after glucose loading in humans. An intravenous injection of 18 F-FP-CIT was administered after infusion of glucose or placebo, and the emission data were acquired over 90 min in 38 healthy male participants. DAT availability expressed in terms of binding potential (BPND ) was recorded. The 40-bp variable number of tandem repeats (VNTR) in the 3' untranslated region and two single nucleotide polymorphisms (SNPs), rs2652511 and rs2937639, in the SLC6A3 gene were genotyped. Among the 38 participants, those with a VNTR other than 10R/10R (n = 7) were excluded. The alleles of the two SNPs (rs2652511 and rs2937639) appeared to be inherited together in two fixed combinations (C-G or T-A) in 29 of 31 individuals. The BPND in the ventral striatum (VST), caudate nucleus, and putamen was not significantly different after glucose or placebo loading according to genotype. However, BPND s from the caudate nucleus and putamen of all participants with rs2652511 CT/rs2937639 AG (n = 6) were higher after glucose loading. In conclusion, the SLC6A3 gene polymorphism is associated with the changes in DAT availability after glucose loading. DAT availability after glucose or placebo loading in the VST, caudate nucleus, and putamen did not differ according to the SLC6A3 genotype.

Hedonic Rating of Sucrose Is Sub-Regionally Associated with Striatal Dopamine Transporter in Humans.

BACKGROUND: Eating behavior is determined by both homeostatic and hedonic values. OBJECTIVE: We investigated the association of hedonic value with striatal dopamine transporter (DAT) availability sub-regionally. METHOD: An intravenous bolus injection of 18F-FP-CIT was administered after the infusion of glucose or placebo, and the emission data were acquired over 90 min. DAT availability and binding potential (BPND) were measured via the simplified reference tissue method. Subjects were assessed with sensory taste test of sucrose solutions. The "most liked" sucrose concentration (%) was determined as the hedonic rating for sucrose. RESULTS: Twenty healthy males participated in this study. After glucose loading, BPNDs of putamen significantly increased, and those of caudate nucleus showed the increasing trend, while those of ventral striatum were not significantly different. After glucose loading, the "most liked" sucrose concentration (%) was negatively associated with BPNDs of caudate nucleus and showed the trend of positive association with those from ventral striatum. Slopes of regression lines were significantly different according to the sub-regions of striatum. CONCLUSION: We have highlighted that striatal DAT increased after glucose loading in dorsal striatum, not in ventral striatum. These changes of striatal DAT were sub-regionally associated with the hedonic rating of sucrose from each subject.

Striatal DAT availability does not change after supraphysiological glucose loading dose in humans.

Brain dopamine neurotransmission is regulated by the dopamine transporter (DAT), which drives reuptake of extracellular dopamine into the presynaptic neurons. We hypothesized that the glucose loading dose would affect the striatal DAT availability. An i.v. bolus injection of 18F-FP-CIT was administered after infusion of low-dose glucose (300 mg/kg), high-dose glucose (600 mg/kg) or placebo (normal saline). The emission data were acquired over 90 min in 23 healthy male subjects. Substantial increases of binding potential (BPNDs) from ventral striatum (VST), caudate nucleus, and putamen were observed after low-dose glucose loading (+26.0, +87.0, and +37.8%) and after high-dose glucose loading (+10.4, +51.9, and +22.0%). BPNDs of the caudate nucleus and putamen showed significant differences (P = 0.0472 and 0.0221) after placebo, low-dose glucose, and high-dose glucose loading. BPNDs in the caudate nucleus and putamen after placebo, low-dose glucose, and high-dose glucose loading were positively intercorrelated with each other. In conclusion, striatal DAT changes after physiological glucose loading, but not after supraphysiological glucose loading in humans. DAT availabilities after placebo, low-dose glucose, high-dose glucose loading were correlated to each other in the caudate nucleus and putamen, but not in the VST. Therefore, sub-regional variability in DAT regulatory mechanisms mediated by insulin may exist in humans.

The association of DAT gene methylation with striatal DAT availability in healthy subjects.

BACKGROUND: DNA methylation inhibits gene expression by preventing transcription factors from binding to DNA. Functioning of nigrostriatal dopaminergic neurons is influenced by the expression of the dopamine transporter (DAT), and genetic variations in the gene encoding DAT contribute to differences in reward processing. We aimed to investigate the action of DAT methylation on DAT protein expression measured by positron emission tomography (PET). METHODS: The emission data were acquired over 90 min with 50 frames after injection of 18F-FP-CIT using PET. Binding potentials (BPNDs) of ventral striatum, caudate nucleus, putamen were measured with the simplified reference tissue method. Genomic DNA was extracted from subjects' blood sampling. Methylation of 4 regions in SLC6A3 gene was assessed using bisulfite pyrosequencing. The mean percentage of methylation (%) for each cluster was calculated by taking the average of all CpG site methylation levels measured within the cluster. Subjects were assessed with the Generalized Reward and Punishment Expectancy Scales (GRAPES) that consists of 30 items related with the reward and punishment that individuals expect for their behaviors. RESULTS: Thirty-five healthy males, with an age range between 20 and 30 years, and a mean age of 24.4 ± 2.7 years, were included in this study. The mean percentage of methylation (%) from cluster C showed a trend of positive correlation with DAT availability of ventral striatum (rho = 0.3712, p = 0.0281), not significant after correction for multiple comparisons, and a significant correlation with GRAPES A: reward expectancy scale (rho = 0.7178, p < 0.0001). CONCLUSION: DAT methylation from peripheral blood showed a trend of positive correlation with DAT availability of ventral striatum in healthy subjects; however, it was not significant after correction for multiple comparison. The degrees of methylation from cluster C of DAT in peripheral blood were significantly correlated with reward scales of GRAPES A: reward expectancy scale. The association between DAT methylation and DAT expression needs to be investigated further.

Effect of sex on aging-related decline of dopamine transporter in healthy subjects.

OBJECTIVE: Aging decreases dopamine transporter (DAT) availability of striatum both in humans and rodents. We aimed to investigate the relationship of DAT availabilities from ventral striatum, caudate nucleus, and putamen with aging in healthy subjects. METHODS: 123I-FP-CIT single photon emission computed tomography (SPECT) was performed in all subjects. Specific binding of 123I-FP-CIT regarding DAT was calculated using a volume-of-interest-based analysis of ventral striatum, caudate nucleus, putamen. The cerebellum was chosen as a reference region. Specific binding ratios (SBRs) were calculated as follows: SBR = (target- cerebellum)/cerebellum. RESULTS: A total of 166 healthy subjects (109 males and 57 females) were included in this study. SBRs of ventral striatum, caudate nucleus, and putamen were negatively correlated with age. In young males, SBRs of ventral striatum and putamen were not correlated with aging. However, SBRs of caudate nucleus showed the trend toward negative correlation with age in the young group. In old males, SBR of caudate nucleus was negatively correlated with age and SBR of ventral striatum showed a trend toward negative correlation with age. Slopes of regression lines were not significantly different according to age groups in ventral striatum, caudate nucleus, or putamen. SBRs of ventral striatum, caudate nucleus, and putamen were negatively correlated with age in young females, but not in old females. Interestingly, slopes of regression line were significantly different between young and old females in ventral striatum, caudate nucleus, and putamen. CONCLUSIONS: We have shown that slopes of regression lines of DAT availabilities and age were significantly different between young and old subjects in females, not in males. Therefore, sex has an impact on aging-related decline of striatal DAT availability.

Striatal dopamine transporter changes after glucose loading in humans.

AIMS: The dopamine transporter (DAT) actively translocates dopamine that is released from the presynaptic neurons across the membranes of nerve terminals into the extracellular space. We hypothesized that glucose loading-induced changes in striatal DAT levels could be associated with food intake in humans. MATERIALS AND METHODS: An intravenous bolus injection of 18 F-FP-CIT was administered after infusion of glucose or placebo (normal saline), and emission data were acquired over 90 minutes in 33 healthy males. For a volume-of-interest-based analysis, an atlas involving sub-striatal regions of ventral striatum (VST), caudate nucleus and putamen was applied. DAT availability and binding potential (BPND ) were measured using a simplified reference tissue method with cerebellum as the reference. RESULTS: The glucose-loaded BPND from the VST negatively correlated with body mass index (BMI), whereas the placebo-loaded BPND from the VST did not. After loading with glucose, there were substantial increases in BPND s: 18.3%, 71.7% and 34.0% on average in the VST, caudate nucleus and putamen, respectively. CONCLUSION: Striatal DAT changes after glucose loading, and BMI is associated with glucose-loaded DAT availability, not with placebo-loaded DAT availability. DAT might have a role in the reward system of eating behavior.

Prediction of future weight change with dopamine transporter in patients with Parkinson's disease.

Fluctuating body weight is a commonly reported nonmotor feature in patients with Parkinson's disease (PD). We hypothesised that striatal dopamine transporter (DAT) density at the time of diagnosis might play an important role in weight regulation in patients with PD. DAT density was measured from 123I-FP-CIT single-photon emission computed tomography. Region-of-interest analyses were performed to measure the specific binding of 123I-FP-CIT to DAT, and the putamen-to-caudate nucleus ratio (PCR) was calculated. Body weight was measured at baseline (W0) and at 48 months (W48). We classified subjects into three groups: weight loss, stable, and weight gain. In final analyses, 163 patients (106 men, 57 women) were included. PCR significantly differed by group in men, but not in women or across all patients. In men, PCR was slightly negatively associated with the percentage change in weight. No such correlation was found across all patients or in women. In univariate and multivariate logistic regression analyses, low PCR was associated with future weight gain in men with PD but not in women. In conclusion, striatal DAT availability at the time of diagnosis could predict subsequent weight change in men with PD.

Prediction of future weight change with the dopamine transporter.

The brain plays a critical role in controlling and inhibiting pre-potent responses to foods. We investigated the predictive value of dopamine transporter (DAT) availability in the striatum of healthy subjects using 123I-FP-CIT single-photon emission computed tomography (SPECT). In total, 84 participants with available data on their weight for the 60 months after SPECT were included. Specific binding of 123I-FP-CIT to DAT was calculated using region-of-interest analysis, and the putamen-to-caudate nucleus ratio (PCR) was determined. After comparing the weights at 12, 24, 36, 48, and 60 months after SPECT with the baseline weight, we categorized participants into three groups: weight gain (> 5%), stable (-5%-5%), and weight loss (< -5%). PCRs of the weight-loss, stable, and weight-gain groups significantly differed at 36 and 48 months. According to post-hoc analysis, PCRs were lower in the weight gain group at 36 and 48 months compared with at the remaining time points. Overall, our results suggest that PCRs calculated based on DAT availability could be used to predict future weight changes. It is possible that the interactions between the caudate nucleus and the putamen, rather than the individual behavior of each structure, might play an important role in weight regulation. Further studies are needed to investigate the time-dependence of the predictive value of DAT.

Correlations between striatal dopamine transporter distribution, glucose metabolism and clinical symptoms in Parkinson′s disease / 中华核医学与分子影像杂志

Objective@#To investigate the correlations among striatal dopamine transporter (DAT) distribution, glucose metabolism and Parkinson′s disease (PD) clinical symptoms.@*Methods@#Twenty-five clinically confirmed idiopathic PD patients (17 males, 8 females, age: (59.8±9.2) years) who underwent 11C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane (CFT) and 18F-fluorodeoxyglucose (FDG) PET imaging from January 2015 to December 2016 were reviewed. The detailed clinical scores were systematically collected from all patients. Correlations between DAT distribution, glucose metabolism and clinical symptoms were evaluated at global and voxel levels using Pearson correlation analysis.@*Results@#There were significantly positive correlations between the PD-related pattern (PDRP) value and unified PD rating scale (UPDRS) motor scores, non-motor symptoms scale (NMSS) scores, activity of daily living scale (ADL) scores (r values: 0.580, 0.522, 0.557, all P<0.05). The CFT uptake of ipsilateral caudate nucleus, anterior putamen, and posterior putamen were negatively correlated with UPDRS motor scores (r values: -0.496, -0.492, -0.457, all P<0.05), while those had no significant correlations with NMSS scores (r values: -0.420, -0.402, -0.355, all P>0.05). The CFT uptake of ipsilateral caudate nucleus and anterior putamen were negatively correlated with ADL scores (r values: -0.502, -0.522, both P<0.05). There were no significant correlations between CFT uptake in contralateral striatal, anterior putamen, posterior putamen and PDRP values, UPDRS motor scores, NMSS scores and ADL scores(r values: from -0.466 to -0.129, all P>0.05). The presence of the significant correlations between UPDRS motor scores, ADL scores and the CFT radioactive count were confirmed in left caudate nucleus and left putamen (r values: from -0.90 to -0.47, all P<0.05). The metabolic PET imaging disclosed a set of brain regions correlating with the clinical symptoms. The presence of significant correlations between the metabolic PET imaging and CFT uptake were confirmed in bilateral caudate nucleus (r values: 0.47-0.90, both P<0.01), precentral gyrus and insula (r values: -0.90 to -0.47, all P<0.01).@*Conclusion@#The correlations between DAT distribution, glucose metabolism and PD clinical symptoms are complicated, which promote the understanding in the proper application of dopaminergic and metabolic PET imaging in PD and offer more evidences in PD pathophysiological mechanisms.

Correlations between striatal dopamine transporter distribution, glucose metabolism and clinical symptoms in Parkinson's disease / 中华核医学与分子影像杂志

Objective To investigate the correlations among striatal dopamine transporter (DAT) distribution,glucose metabolism and Parkinson's disease (PD) clinical symptoms.Methods Twenty-five clinically confirmed idiopathic PD patients (17 males,8 females,age:(59.8± 9.2) years) who underwent 11 C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl) tropane (CFT) and 18 F-fluorodeoxyglucose (FDG) PET imaging from January 2015 to December 2016 were reviewed.The detailed clinical scores were systematically collected from all patients.Correlations between DAT distribution,glucose metabolism and clinical symptoms were evaluated at global and voxel levels using Pearson correlation analysis.Results There were significantly positive correlations between the PD-related pattern (PDRP) value and unified PD rating scale (UPDRS) motor scores,non-motor symptoms scale (NMSS) scores,activity of daily living scale (ADL) scores (r values:0.580,0.522,0.557,all P＜0.05).The CFT uptake of ipsilateral caudate nucleus,anterior putamen,and posterior putamen were negatively correlated with UPDRS motor scores (r values:-0.496,-0.492,-0.457,all P＜0.05),while those had no significant correlations with NMSS scores (r values:-0.420,-0.402,-0.355,all P＞0.05).The CFT uptake of ipsilateral caudate nucleus and anterior putamen were negatively correlated with ADL scores (r values:-0.502,-0.522,both P＜0.05).There were no significant correlations between CFT uptake in contralateral striatal,anterior putamen,posterior putamen and PDRP values,UPDRS motor scores,NMSS scores and ADL scores(r values:from-0.466 to-0.129,all P＞0.05).The presence of the significant correlations between UPDRS motor scores,ADL scores and the CFT radioactive count were confirmed in left caudate nucleus and left putamen (r values:from-0.90 to-0.47,all P＜0.05).The metabolic PET imaging disclosed a set of brain regions correlating with the clinical symptoms.The presence of significant correlations between the metabolic PET imaging and CFT uptake were confirmed in bilateral caudate nucleus (r values:0.47-0.90,both P＜0.01),precentral gyrus and insula (r values:-0.90 to-0.47,all P＜0.01).Conclusion The correlations between DAT distribution,glucose metabolism and PD clinical symptoms are complicated,which promote the understanding in the proper application of dopaminergic and metabolic PET imaging in PD and offer more evidences in PD pathophysiological mechanisms.

Effect of rs3910105 in the Synuclein Gene on Dopamine Transporter Availability in Healthy Subjects.

PURPOSE: The present study investigated associations between dopamine transporter (DAT) availability and α-synuclein levels in cerebrospinal fluid, as well as synuclein gene (SNCA) transcripts, and the effect of single nucleotide polymorphism of SNCA on DAT availability in healthy subjects. MATERIALS AND METHODS: The study population comprised healthy controls who underwent ¹²³I-FP-CIT single-photon emission computed tomography screening. Five SNCA probes were used to target the boundaries of exon 3 and exon 4 (SNCA-E3E4), transcripts with a long 3'UTR region (SNCA-3UTR-1, SNCA-3UTR-2), transcripts that skip exon 5 (SNCA-E4E6), and the rare short transcript isoforms that comprise exons 1-4 (SNCA-007). RESULTS: In total, 123 healthy subjects (male 75, female 48) were included in this study. DAT availability in the caudate nucleus (p=0.0661) and putamen (p=0.0739) tended to differ according to rs3910105 genotype. In post-hoc analysis, DAT availability in the putamen was lower in subjects of TT genotype than those of CC/CT (p=0.0317). DAT availability in the caudate nucleus also showed a trend similar to that in the putamen (p=0.0597). Subjects of CT genotype with rs3910105 showed negative correlations with DAT availability in the putamen with SNCA-E3E4 (p=0.037, rho=-0.277), and SNCA-E4E6 (p=0.042, rho=-0.270), but not those of CC/TT genotypes. CONCLUSION: This is the first study to investigate the association of rs3910105 in SNCA with DAT availability. rs3910105 had an effect on DAT availability, and the correlation between DAT availability and SNCA transcripts were significant in CT genotypes of rs3910105.

Correlation between the availability of dopamine transporter and olfactory function in healthy subjects.

OBJECTIVES: Olfactory dysfunction in Parkinson's disease is usually prodromal to other symptoms. In this study, we aimed to explore the association of olfactory function with the availabilities of striatal dopamine transporter (DAT) in healthy subjects. METHODS: Data used in the preparation of this article were obtained from Parkinson's Progression Markers Initiative database ( www.ppmi-info.org/data ). The study population consisted of healthy controls with screening 123I-FP-CIT single photon emission tomography (SPECT). University of Pennsylvania Smell Identification Test (UPSIT) was assessed to evaluate the olfactory function. RESULTS: Totally, 181 healthy subjects (117 male, 64 female) with 123I-FP-CIT SPECT data were included in this study. Specific binding ratios (SBRs) of the caudate nucleus (rho = -0.4217, p < 0.0001), putamen (rho = -0.2292, p = 0.0019), and striatum (rho=-0.3425, p < 0.0001) showed a reduction with ageing. SBRs of the caudate nucleus, putamen, and striatum were positively correlated with UPSIT (rho = 0.3716, p < 0.0001; rho = 0.3655, p < 0.0001; rho = 0.3880, p < 0.0001). After controlling for age by partial correlation, SBRs of the caudate nucleus, putamen, and striatum showed an influence on UPSIT (rho = 0.3288, p < 0.0001; rho = 0.3374, p < 0.0001; rho = 0.3511, p < 0.0001). CONCLUSION: Olfactory function is associated with the availability of striatal DAT independent of age in healthy subjects. KEY POINTS: • Olfactory dysfunction in Parkinson's disease is prodromal to other symptoms. • The availability of dopamine transporter showed a reduction with ageing. • Olfactory function is associated with the availability of dopamine transporter.

Effect of rs3910105 in the Synuclein Gene on Dopamine Transporter Availability in Healthy Subjects

PURPOSE: The present study investigated associations between dopamine transporter (DAT) availability and α-synuclein levels in cerebrospinal fluid, as well as synuclein gene (SNCA) transcripts, and the effect of single nucleotide polymorphism of SNCA on DAT availability in healthy subjects. MATERIALS AND METHODS: The study population comprised healthy controls who underwent 123I-FP-CIT single-photon emission computed tomography screening. Five SNCA probes were used to target the boundaries of exon 3 and exon 4 (SNCA-E3E4), transcripts with a long 3′UTR region (SNCA-3UTR-1, SNCA-3UTR-2), transcripts that skip exon 5 (SNCA-E4E6), and the rare short transcript isoforms that comprise exons 1–4 (SNCA-007). RESULTS: In total, 123 healthy subjects (male 75, female 48) were included in this study. DAT availability in the caudate nucleus (p=0.0661) and putamen (p=0.0739) tended to differ according to rs3910105 genotype. In post-hoc analysis, DAT availability in the putamen was lower in subjects of TT genotype than those of CC/CT (p=0.0317). DAT availability in the caudate nucleus also showed a trend similar to that in the putamen (p=0.0597). Subjects of CT genotype with rs3910105 showed negative correlations with DAT availability in the putamen with SNCA-E3E4 (p=0.037, rho=−0.277), and SNCA-E4E6 (p=0.042, rho=−0.270), but not those of CC/TT genotypes. CONCLUSION: This is the first study to investigate the association of rs3910105 in SNCA with DAT availability. rs3910105 had an effect on DAT availability, and the correlation between DAT availability and SNCA transcripts were significant in CT genotypes of rs3910105.

Multiple modalities PET/CT neuroimaging for the diagnosis of Parkinson's disease and multiple system atrophy: statistical parametric mapping analysis / 中华神经科杂志

Objective To investigate the topographic distributions of dopamine transporter (DAT),dopamine D2 receptor and glucose in Parkinson's disease (PD) and multiple system atrophy (MSA) using positron emission tomography/computed tomography (PET/CT) scanning and statistical parametric mapping (SPM) analysis.Methods Seventy subjects (39 PD patients,15 MSA patients and 16 normal controls) who came from People's Liberation Army General Hospital from September 2013 to November 2015 underwent DAT,D2 receptor and glucose brain PET/CT scans using 11 C-methyl-N-2-β-carbomethoxy-3-β-(4-fluorophenyl) tropane (11C-β-CFT),11C-raclopride and 18F-fluorodeoxyglucose (18 F-FDG) as radiotracers,respectively.The uptake patterns were analyzed using SPM software.Results Striatal DAT binding decreased in the putamen in PD patients compared with controls (Z =5.21-5.77,P =0.002-0.016).D2 receptor showed no significant differences.However,glucose uptake decreased in cingulate gyrus(Z =4.51-4.67,P =0.010-0.017).For MSA patients,both DAT and D2 receptor binding decreased in the putamen(Z =2.13-3.42,P =0.000-0.016).Glucose uptake decreased in the bilateral putamen,cerebellum and part of frontal temporal lobes (Z =1.86-3.75,P =0.000-0.032).Conclusion Multiple modalities PET/CT scans using the ligands 11 C-β-CFT,11C-raclopride,and 18F-FDG are valuable in diagnosis of MSA and differential diagnosis of MSA from PD.

Assessment of effects of 7,8-dihydroxyflavone on the striatum in normal cynomolgus monkeys with 99TCm-TRODAT-1 SPECT/CT imaging / 中华核医学与分子影像杂志

Objective To assess the effects of 7,8-dihydroxyflavone (7,8-DHF) on the striatum (ST) in normal cynomolgus monkeys using 99Tcm-TRODAT-1 imaging.Methods A total of six healthy female cynomolgus monkeys were included in this study.Three of them were fed with normal food (control group),and the other three were given oral administration of 7,8-DHF in addition to normal food (experimental group).The SPECT/CT imaging was performed at different time after 99Tcm-TRODAT-1 injection.The ROI of ST was drawn on images of 3 consecutive transverse slices that could be visualized best.The cerebellum (CB) was taken as the background reference area.The radioactivity uptake ratios of ST/CB at 1,3,4 and 5 h were calculated respectively.Paired-t test was used to analyze the data.Results ST radioactive uptake ratios showed continuing increase on the delay images.ST/CB uptake ratios of the control group at 1,3,4 and 5 h were 1.43±0.04,1.82±0.06,2.04±0.12,2.42±0.23,respectively,and those of the experimental group were 1.35±0.08,2.40±0.09,2.74±0.13 and 3.25±0.15 respectively.There was no significant difference between the two groups at 1 h (t =2.57,P＞0.05),while ST/CB uptake ratios of the experimental group at 3,4 and 5 h were significantly higher (t values:2.77,2.87 and 2.92,all P＜0.05).Conclusion 99Tcm-TRODAT-1 SPECT/CT imaging can be used to assess the DAT activation effect by 7,8-DHF on ST of cynomolgus monkeys.

Classic Studies on the Interaction of Cocaine and the Dopamine Transporter.

The dopamine transporter is responsible for recycling dopamine after release. Inhibitors of the dopamine transporter, such as cocaine, will stop the reuptake of dopamine and allow it to stay extracellularly, causing prominent changes at the molecular, cellular, and behavioral levels. There is much left to be known about the mechanism and site(s) of binding, as well as the effect that cocaine administration does to dopamine transporter-cocaine binding sites and gene expression which also plays a strong role in cocaine abusers and their behavioral characteristics. Thus, if more light is shed on the dopamine transporter-cocaine interaction, treatments for addiction and even other diseases of the dopaminergic system may not be too far ahead. As today's ongoing research expands on the shoulders of classic research done in the 1990s and 2000s, the foundation of core research done in that time period will be reviewed, which forms the basis of today's work and tomorrow's therapies.

Subchronic administration of short-acting naltrexone has no effect on striatal dopamine transporter availability, food intake or body weight gain in rats.

The opioid receptor antagonist naltrexone is successfully used in the treatment of opioid and alcohol dependence. However, questions have been raised about possible anhedonic side effects, because the opioid system is directly involved in hedonic responses to natural rewarding activities, possibly due to its indirect effects on the striatal dopamine transporter (DAT). In order to test this hypothesis, 30 rats were randomized to either a 10-day treatment with 3 mg/kg short-acting naltrexone or vehicle. No significant differences between the groups were found in striatal DAT availability, cumulative food intake (for 48 or 72 h), body weight gain and abdominal fatpad weight. Thus, the results of this study suggest that (sub)chronic treatment with short-acting naltrexone does not induce possible anhedonic effects. However, it cannot be ruled out the anhedonic effect of naltrexone is only short-lived and thus not detected in the current study. Therefore, future studies are needed to study possible acute anhedonic effects at several time points shortly after short-acting naltrexone administration and to directly compare the possible anhedonic effects of long-acting with those of short-acting opioid antagonists.