Dopamine in the prefrontal cortex plays multiple roles in the executive function of patients with Parkinson's disease

Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive impairment.One common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive functioning.Executive functions help us plan,organize,and control our actions based on our goals.The brain area responsible for executive functions is called the prefrontal co rtex.It acts as the command center for the brain,especially when it comes to regulating executive functions.The role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called dopamine.However,little is known about how dopamine affects the cognitive functions of patients with Parkinson’s disease.In this article,the authors review the latest research on this topic.They start by looking at how the dopaminergic syste m,is alte red in Parkinson’s disease with executive dysfunction.Then,they explore how these changes in dopamine impact the synaptic structure,electrical activity,and connection components of the prefrontal cortex.The authors also summarize the relationship between Parkinson’s disease and dopamine-related cognitive issues.This information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson’s disease.

Preliminary clinical application of dopamine transporter imaging with technetium-99m TRODAT-1 and SPECT on the early and differential diagnosis of Parkinson's Disease

The aim of the study was to demonstrate the degeneration of the dopaninergic nigrostriatal pathway in Parkinson's disease(PD) and Essential Tremor (ET) by using the cocaine derivative 99mTc-TRODAT-1 SPECT and correlate the findings to the clinical severities (Hoehn and Yahr scale, H/Y). 28 patients with idiopathic Parkinson's disease, 10 patients with Essential Trenor and 19 healthy volunteers were investigated. The acquisition were performed 3 h postinjection of 99mTc-TRODAT-1, ROIs were drawn over the images of striatum and cerebellum, and ratios of striatum to cerebellar(ST/CB) were calculated. Ratios differed significantly between PD and controls, but ratios didn't show significant difference between ET patients and controls. A significant correlation didn't exist between ratios and clinical severities. Hemiparkinson's patients revealed significantly diminished 99mTc-TRODAT-1 binding not only clinically affected but unaffected side. Our findings indicated that 99mTc-TRODAT-1 SPECT is not only a reliable method to discriminate between PD and controls but also a useful tool for differential diagnosis in clinically unclear cases such as ET resembling PD.

Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

Animal biodistribution, safety and validation study of dopamine transporter PET imaging agent ^(18)F-FECNT

This work was to investigate the pharmacologic characteristics of 18F-FECNT (2β-carbomethoxy-3β- (4-chlorophenyl)-8-(2-[18F]fluoroethyl)nortropane) as a dopamine transporter (DAT) PET imaging agent. Its partition coefficients were determined in n-octanol and phosphate buffer (PB) (pH 7.0 and pH 7.4). 6-Hydroxydopamine (6-OHDA) left-sided lesioned Parkinsonian rats were established and validated by rotational behavior tests. Biodistribution in vivo in mice, autoradiography in normal and hemi-Parkinsonian rat brains, and toxicity test were performed. The results showed that partition coefficients were 34.14 (pH 7.0) and 56.41 (pH 7.4), respectively. Biodistribution exhibited rapid uptake and favorable retention in the mice brains. The major radioactivity was metabolized by the hepatic system. The autoradiography showed that 18F-FECNT was highly concentrated in striatum, and that the left and the right striatal uptake were symmetrical in normal SD rat brains. In left-sided lesioned PD rat brains, the striatal uptake of 18F-FECNT bilaterally decreased in comparison with normal rats. No significant uptake was visible in the 6-OHDA lesioned-sided striatal areas. The results demonstrated that 18F-FECNT binds to DAT was specific. Toxicity trial displayed that the acceptable dose per kilogram to mice was 625 times greater than that to human. These indicate that 18F-FECNT is a potentially safe and useful DAT PET imaging agent in the brain.

Feasibility of ^(99m)Tc-TRODAT-1 Micro-SPECT imaging of dopamine transporter in animal retinas

In this paper,^(99m)Tc-TRODAT-1 Micro-SPECT (single-photon emission computed tomography) was used for imaging dopamine transporter (DAT) in retinas and to investigate the changes of DAT in retinas of guinea pigs with form deprivation myopia.Pigmented guinea pigs aged 3 weeks were derided into form deprivation myopia (FDM) group (n=6) and normal control group (n=6).The test group wore translucent goggles randomly for 4 weeks, and both groups underwent biometric measurement (refraction and axial length) before and after the experiment. Micro-SPECT retinas imaging was performed at the 4^(th) week after injection of ^(99m)Tc-TRODAT-1.The retinas were clearly resolved in the images.The ratio of ^(99m)Tc-TRODAT-1 uptake in the myopic retinas (11.55±2.80) was 3.64±1.40 lower than that in the control eye (15.20±1.98),and 2.35±1.05 lower than that in the fellow eyes (13.90±2.04).The results showed that ^(99m)Tc-TRODAT-1 Micro-SPECT eye imaging can be used to trace the distribution and changes of DAT in retina,and DAT in the myopic retinas were lower than that in the normal control eyes and fellow eyes.Micro-SPECT may provide a new approach for further studies on the role of dopamine system in the experimental myopia.

Effects of compound rehmannia formula on dopamine transporter content in the corpus striatum of Parkinson's disease rats treated with levodopa

Long-term application of levodopa （L-3, 4-dihydroxyphenylalanine, L-DOPA） for Parkinson＇s disease can lead to adverse effects and reduce the amount of dopamine transporter （DAT） in the corpus striatum. The present study attempted to vedfy whether increasing the amount of DAT can reduce the adverse effects of L-DOPA. The specific radioactive uptake value of DAT in the corpus striatum of the lesioned hemisphere was significantly decreased, but was significantly increased following administration of compound rehmannia formula [Radix rehmanniae preparata （prepared rehmannia root）, Concha margantifera usta （nacre）, Radix paeoniae alba （white peony alba）, Radix salviae miltiotThizae （Danshen root）, Scorpio （scorpion）, green tea] for 4 weeks. The changes in DAT 1251-beta-carbomethoxy-3 beta-（4-iodophenyl） tropane autoradiography were consistent with those in radioactivity. The results revealed that the compound rehmannia formula can reduce the adverse effects of L-DOPA in treating Parkinson＇s disease, possibly by increasing the amount of DAT.

Degree of dopaminergic degeneration measured by ^(99m)Tc-TRODAT-1 SPECT/CT imaging

To prevent and treat Parkinson＇s disease in its early stages,it is essential to be able to detect the degree of early dopaminergic neuron degeneration.Dopamine transporters（DAT） in the striatum regulate synaptic dopamine levels,and striatal ^99mTc-TRODAT-1 single-photon emission computed tomography（-SPECT） imaging is a marker for presynaptic neuronal degeneration.However,the association between the degree of dopaminergic degeneration and in vivo ^99mTc-TRODAT-1 SPECT imaging is unknown.Therefore,this study investigated the association between the degree of 6-hydroxydopamine（6-OHDA）-induced dopaminergic degeneration and DAT imaging using^99mTc-TRODAT-1 SPECT in rats.Different degrees of nigrostriatal dopamine depletion were generated by injecting different doses of 6-OHDA（2,4,and 8 μg） into the right medial forebrain bundle.The degree of nigrostriatal dopaminergic neuron degeneration was assessed by rotational behavior and immunohistochemical staining.The results showed that striatal ^99mTc-TRODAT-1 binding was significantly diminished both in the ipsilateral and the contralateral sides in the 4 and 8 μg 6-OHDA groups,and that DAT ^99mTc-TRODAT-1 binding in the ipsilateral striatum showed a high correlation to apomorphine-induced rotations at 8 weeks post-lesion（r = –0.887,P 〈 0.01）.There were significant correlations between DAT ^99mTc-TRODAT-1 binding in the ipsilateral striatum and the amount of tyrosine hydroxylase immunoreactive neurons in the ipsilateral substantia nigra in the 2,4,and 8 μg 6-OHDA groups at 8 weeks post-lesion（r = 0.899,P 〈 0.01）.These findings indicate that striatal DAT imaging using ^99mTc-TRODAT-1 is a useful technique for evaluating the severity of dopaminergic degeneration.

Pharmacological studies of dopamine transporter imaging agent ^(125/131)I-β-CIT

To prepare 125/131I-β-CIT (2β-carbomethoxy-β- (4-iodophenyl)tropane) as an imaging agent for dopamine transporter (DAT), the labeling method from tributylstannyl precursor with peracetic acid has been reported in this article. The radio-chemical purity (RCP) of the labeled compound was over 95% determined by HPLC and TLC. The stability, partition coefficients were also determined. The pharmacological studies of the imaging agent were performed in rats, mice, rabbits and normal monkey. The ligand showed preferable uptake in brain (1 .9%ID/organ in rats and 4.5%ID/organ in mice at 5 min). The ratios of striatum/cerebellum, hippocampus/cerebellum and cortex/cerebellum were 28.9, 3.97 and 4.75 at 6 h in rats, and 8.52, 2.99 and 3.06 at 6h in mice, respectively. In monkey brain imaging the ratios of striatum/frontal cortex (ST/FC) and striatum/occipital cortex (ST/OC) were 5.14 and 5.97 at 4 h, respectively. All of above showed the high affinity of the ligand to DAT. The compound was primarily metabo lized in liver because the hepatic uptake was much higher than other organs (75.4%ID/organ at 18h). The half-life of blood elimination was 5min The dose received by mice was 2500 times as high as that received by human in the test of undue toxicity, which evaluated the safety of the agent. All the results suggest that fl-CIT can be used as a potential DAT imaging agent.

Blunt dopamine transmission due to decreased GDNF in the PFC evokes cognitive impairment in Parkinson’s disease

Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson’s disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson’s disease. We then established a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson’s disease.

Effect of variable number of tandem repeats polymorphism in the human dopamine transporter gene on conflict information processing according to event-related potential

The dopamine transporter （DAT） is responsible for dopamine reuptake from the synaptic cleft. A variable number of tandem repeats polymorphism in the DAT gene is related to DAT availability and has been associated with cognition. With the advantage of high-time resolution, event-related potential is an important method to study the time course of human information processing. Previous results have suggested that dopamine exhibits a close relationship with conflicting information processing. Therefore, the present study assumed that conflicting information processing could be influenced by DAT variable number of tandem repeats polymorphism. To confirm this, the present study analyzed the influence of DAT genotypes on N270, which is presumed to reflect neural activity of conflict information processing in young healthy adults. A S1-S2 matching task was performed in healthy adults with 10/10 genotype （n = 14） and 10/9 genotypes （n = 14）, respectively, when event-related potentials were recorded. Results demonstrated that subjects with the 10/10 genotype exhibited shorter N270 latency and quicker reaction times compared with subjects with the 10/9 genotype. There were no differences in N270 amplitude between the two genotypes. These results suggested that 10/10 genotype subjects more efficiently processed conflict information.

Novel translational rat models of dopamine transporter deficiency

Dopamine （DA） is one of the brain＇s fundamental neurotransmitters. Despite the fact that the dopaminergic synapses constitute less than 1% of all brain synapses, DA is implicated in a number of critical physiological functions and in the pathogenesis of important psychiatric diseases such as schizophrenia, attention-deficit/hyperactivity disorder （ADHD）, Parkinson＇s disease （PD） and others.

PROPOFOL DECREASES ^(125)I-β-CIT BINDING TO THE DOPAMINE TRANSPORTER

Objective To determine the changes of brain dopamine transporter in mice receiving propofol anesthesia, 125I-β-CIT binding sites were observed at different time course. Methods 1. Twenty-seven normal Kunming mice were randomizedly divided into 3 groups (n = 9 ) and received intraperitoneal injection of propofol 100, 200 mg/kg and 10% intralipid (as control ) respetively. The time of losing righting reflex and displaying excitatory symptoms were recorded within 10min after administration. 2. Sixty Kunming mice were randomizedly assigned into 2 groups (n = 30 ). The mice were given 125I-β-CIT intravenously and propofol 200mg/kg or 10% intralipid (as control ) intraperitoneally. Five mice in every group were killed at different time course and their brain removed to isolate cerebellar, hypothalamus, striatum and cerebral cones. After weighting brain tissues, the radioactivity of 125I-β-CIT in different brain tissue was measured. Results 1. The time of losing righting reflex wes reduced from 319. 167 ± 88. 228s in proud 100mg/kg group to 231. 667 ± 46. 233s in propofol 200mg/kg group, and it fell from 193. 75 ± 27. 233s to 145. 556 ± 27. 437s for presenting excitatory activity. 2. Propofol intraperitoneal groups significantly decreed the combination of 125I-β-CIT and dopamine transporter in the striatum (P< 0. 01 ) and cerebral cortex (P < 0. 05) 120min after injection of propofol compared with the control group. But propofol increased the binding (P< 0. 05 ) in the striatum 30min after injection. theclusion The inhibitive effect of propofol on dopamine transporter to uptake dopamine in mice brain may contribute to some anesthetic mechanisms.

The preclinical pharmacological study of dopamine transporter imaging agent ^(18)F-FP-β-CIT

The paper is to study pharmacologic characteristics of 18F-FP-β-CIT (18F-N-(3-fluoropropyl)-2β-carbomethoxy-3β- (4-iodophenyl)nortropane) as an imaging agent for dopamine transporter. The radiochemical purity of 18F-FP-β-CIT in aqueous solution was over 95% after standing at room temperature for 4h. Biodistribution displayed rapid uptake in rat brain (1.375 %ID/organ at 5min and 0.100 %ID/organ at 180 min) and the striatal uptake was 1.444, 0.731, 0.397, 0.230 and 0.146 %ID/g at 5, 30, 60, 120 and 180 min, respectively. The values of striatum/cerebellum, striatum /frontal cortex and striatum / hippocampus in rat's brain at 30 min were 3.38, 2.17 and 2.40 respectively. The uptake in striatum can be blocked by β-CFT, suggesting that 18F-FP-β-CIT binds to DAT peculiarly. The compound was rapidly cleared from monkey's blood. The striatal uptake was bilaterally decreased in the left-sided lesioned PD rats, compared with normal control. Brain PET imaging studies in normal monkey showed that 18F-FP-β-CIT was concentrated in striatum. The test of undue toxicity showed that the dose received by mice was 1250 times as by human, which indicates that 18F-FP-β-CIT is very safe. So 18F-FP-β-CIT is a promising PET imaging agent for DAT with safety and validity.

静磁场暴露对大鼠抑郁样行为及海马DR2和DAT表达的影响

目的 探讨静磁场暴露对大鼠抑郁样行为及海马多巴胺受体2(DR2)和多巴胺转运体(DAT)表达的影响。方法 将Wistar大鼠置于自制鼠笼中,采用超导磁体暴露源进行全身暴露,暴露强度为50 mT、100 mT、200 mT,时间为1 h/d,连续暴露15 d或30 d。采用糖水试验、脑电生理检测大鼠在不同强度磁场暴露后行为学及脑电改变,而后采用免疫组化法检测大鼠海马区DR2和DAT的表达并进行定量分析。结果 200 mT静磁场暴露30d致大鼠糖水偏爱指数明显降低;三个暴露组大鼠脑电异常,其中高强度暴露组改变最为显著;免疫组化结果显示,静磁场暴露第10 d, 100 mT和200 mT暴露组海马DAT表达显著升高,暴露第15 d,各暴露组DAT表达均显著升高。暴露第15 d,各暴露组大鼠海马DR2表达均显著降低。结论 静磁场暴露导致大鼠抑郁样行为及脑电改变,海马区DR2和DAT表达异常可能与其抑郁样行为发生相关。

癫痫共患注意缺陷多动障碍患儿外周血DRD2 DAT基因表达与焦虑 抑郁情绪的关系

目的 探究癫痫共患注意缺陷多动障碍(ADHD)患儿外周血多巴胺D2受体(DRD2)、多巴胺转运体(DAT)基因表达与焦虑、抑郁情绪的关系。方法 选取2018-01—2021-01开封市儿童医院收治的74例癫痫患儿为疾病组,其中癫痫患儿共患ADHD为A组(n=37),单纯癫痫患儿为B组(n=37)。另选同时段本院治疗的抽动障碍(TD)患儿为对照组(n=35)。观察患儿心理状态[汉密尔顿焦虑量表(HAMA)和抑郁自评量表(SDS)评分],检测其外周血DRD2、DAT基因表达;Pearson相关法分析DRD2、DAT基因表达与患儿心理状态评分的相关性;Logistic回归分析癫痫共患ADHD患儿焦虑、抑郁发生的影响因素。结果 3组患儿SDS评分、HAMA评分及DAT mRNA、DRD2 mRNA表达有统计学差异(P<0.05);外周血DAT、DRD2基因表达均与SDS评分、HAMA评分均呈正相关(r=0.439、0.479、0.520、0.516,P均<0.05);Logistic回归分析显示DAT、DRD2表达升高是癫痫共患ADHD患儿焦虑、抑郁的影响因素(P<0.05)。结论 癫痫共患ADHD患儿外周血DAT、DRD2基因表达升高更容易发生焦虑、抑郁情绪,有临床价值。

基于CFN-MPS200模块的[^(18)F]氟-FP-CIT合成与质量分析

目的:合成多巴胺转运蛋白显像剂[^(18)F]氟-氮-(3-氟丙基)-2β-甲酯基-3β-(4'-碘苯基)去甲基托烷([^(18)F]氟-FP-CIT),并进行质量控制分析。方法:^(18)F^(-)与氮-(3'-甲基黄酰氧基丙基)-2β-甲酯基-3β-(4'-碘苯基)去甲托烷2β-甲酯基-3β-(4-碘苯基)降托烷发生亲核取代以获得产品。采用高效液相色谱进行分离,再以C_(18)小柱进行纯化,得到成品。结果:不校正产率(EOS)≥15%(n=8),合成时间<60 min,产品的放化纯度>98%。结论:[^(18)F]氟-FP-CIT可以用CFN-MPS200多功能合成模块全自动稳定合成,并有较高的工艺稳定性和产率,避免了工作人员被辐照的风险,产品符合GMP要求,满足临床和动物实验研究。

中枢多巴胺系统正电子发射计算机断层扫描显像剂的研究进展

中枢多巴胺系统与多种神经行为障碍的病理生理学有关。一直以来,多巴胺系统正电子发射计算机断层扫描(PET)成像在研究活体大脑中多巴胺生物化学过程上有着重要价值。PET成像的基础是^(11)C、^(18)F等发射正电子的放射性核素标记的显像剂,这些显像剂通过与多巴胺神经系统不同的靶点特异性结合从而反映多巴胺合成、囊泡储存、突触释放和受体结合以及再摄取过程,推动神经病学、精神病学、药物滥用和成瘾以及药物开发的研究进展。本文综述了以氨基酸脱羧酶、多巴胺转运体、多巴胺受体以及囊泡单胺转运体为靶点的^(11)C、^(18)F标记的PET显像剂的研究进展。

脑多巴胺转运蛋白^(99)Tc^m-TRODAT-1显像研究

目的 探讨99Tcm 2 β [N ,N′ 双 (2 巯乙基 )乙撑二胺基]甲基 ,3β (4 氯苯基 )托烷 (TRODAT 1)多巴胺转运蛋白 (DAT)显像剂的生物学行为和体内分布及显像条件。方法 正常志愿者 13例。根据99Tcm TRODAT 1自定制备程序和质量标准 ,制备99Tcm TRODAT 1,放化纯 (Rp) >85 % ,注射量 92 5MBq ml。所有受检者行动态显像、全身显像和断层显像。结果 99Tcm TRODAT 1“弹丸”样静脉注射后约 2min脑内放射性趋向稳定。99Tcm TRODAT 1入脑量仅为 (1 91± 0 4 3) %ID ;放射性主要分布在肝脏 (2 7 6 0± 11 15 ) %ID ,胃肠道 (14 13± 2 2 4 ) %ID ,肺 (11 90± 1 6 7) %ID ;而心肌、肾脏、胆囊、甲状腺分布较少 ,分别为 (4 6 2± 0 98) %ID、(3 2 1± 1 10 ) %ID、(2 37± 0 6 7) %ID和 (0 5 0± 0 0 7) %ID。软组织内分布大量的放射性 ,为 (32 0 0± 11 32 ) %ID。99Tcm TRODAT 1主要从消化系统清除 ,部分经肾脏清除。在99Tcm TRODAT 1注射后 15 0～ 170min断层显像示纹状体和周围脑组织反差最明显。结论 99Tcm TRODAT 1注射液达到临床使用标准。

不同光照模式对豚鼠视网膜多巴胺转运蛋白表达的影响

目的观察不同光照模式对豚鼠眼内多巴胺转运蛋白(DAT)表达的影响。方法选取36只白色3周龄普通级豚鼠,采用随机数字表法将其随机分为10000 lx组、5000 lx组和500 lx组,每组12只,分别接受相应强度的强光、中强光和正常光照射,并在各组内随机分成3个亚组,每组4只,500 lx组分别接受5、20、40 min光照;5000 lx组分别接受2、4、40 min光照;10000 lx组分别接受2、5、20 min光照。各组豚鼠接受光处理后注射99m Tc-TRODAT-1用于SPECT扫描DAT显像,通过Micro-SPECT采集图像数据。采用Micro-CT软件对豚鼠视网膜感兴趣区进行分析,感兴趣区总的计数值用Sum表示,Sum值反映DAT的相对分布量或分布密度。比较光照处理后豚鼠暴露眼和对照眼DAT密度、不同光照强度和不同光照时长下豚鼠双眼DAT密度差值,以及光照强度和光照持续时间对豚鼠DAT聚集的累积效应和交互效应。另取3只豚鼠,光处理后对豚鼠眼部进行连续6 h图像采集,每隔20 min采集1次,每只豚鼠共采集18次,分析豚鼠眼DAT密度随时间的变化趋势。结果500、5000、10000 lx光照强度下暴露眼DAT密度(Sum值)分别为5598.97±3159.38、8636.78±2503.16和7407.39±2053.41,明显高于对照眼的4388.89±2902.90、5981.92±3057.44和5091.32±2039.36,差异均有统计学意义(t=5.31、4.69、11.80,均P<0.001)。500 lx光照强度下,豚鼠暴露眼和对照眼DAT密度差值在不同光照时间组间比较差异有统计学意义(F=14.01,P<0.01),其他光照强度下不同光照时间组间比较差异均无统计学意义(均P>0.05)。光照时间为5 min时,10000 lx组豚鼠暴露眼和对照眼DAT密度差值明显大于500 lx组,差异有统计学意义(t=-13.22,P<0.001),其他光照时长下不同组间比较差异均无统计学意义(均P>0.05)。未发现光照强度、光照时间对DAT密度差值的累积效应和交互效应(均P>0.05)。光照后连续扫描显示,豚鼠视网膜DAT密度随时间延长先上升到峰值,随后逐渐恢复至正常值。结论光照可以引起视网膜DAT分泌增加,即使在中强度或正常光照水平下,也可以起到刺激DAT产生的作用。未发现光照强度和光照时间对视网膜DAT分布和密度的累积效应和交互效应。

帕金森病患者的外周血淋巴细胞DAT功能检测

目的 比较帕金森病 (PD)患者与正常对照组外周血淋巴细胞摄取多巴胺 (DA)量的差异。方法 用密度梯度离心法提取外周血淋巴细胞 ,以 Western blot法检测淋巴细胞上多巴胺转运蛋白 (DAT蛋白 ) ,以液体闪烁记数法检测淋巴细胞摄取 3H-DA的量。结果 Western blot显示在相对分子质量为 660 0 0部位出现一与 DAT蛋白大小相吻合的条带 ;淋巴细胞有摄取 3H-DA的功能 ,且为时间、浓度及 Na+依赖 ;PD患者淋巴细胞摄取 3H-DA的量明显低于正常对照组 (P <0 .0 5 )。结论 检测 PD患者外周血淋巴细胞摄取3H-DA量与正常对照组之间的差异有可能成为