慢性暴露于多巴胺激动剂会影响帕金森病患者纹状体 D 受体的完整性。

Chronic exposure to dopamine agonists affects the integrity of striatal D receptors in Parkinson's patients.

机构信息

Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK.

Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.

出版信息

Neuroimage Clin. 2017 Aug 24;16:455-460. doi: 10.1016/j.nicl.2017.08.013. eCollection 2017.

Abstract

We aimed to investigate the integrity and clinical relevance of striatal dopamine receptor type-2 (DR) availability in Parkinson's disease (PD) patients. We studied 68 PD patients, spanning from early to advanced disease stages, and 12 healthy controls. All participants received one [C]raclopride PET scan in an OFF medication condition for quantification of striatal DR availability . Parametric images of [C]raclopride non-displaceable binding potential were generated from the dynamic [C]raclopride scans using implementation of the simplified reference tissue model with cerebellum as the reference tissue. PET data were interrogated for correlations with clinical data related to disease burden and dopaminergic treatment. PD patients showed a mean 16.7% decrease in caudate DR and a mean 3.5% increase in putaminal DR availability compared to healthy controls. Lower caudate [C]raclopride BP correlated with longer PD duration. PD patients on dopamine agonist treatment had 9.2% reduced DR availability in the caudate and 12.8% in the putamen compared to PD patients who never received treatment with dopamine agonists. Higher amounts of lifetime dopamine agonist therapy correlated with reduced DRs availability in both caudate and putamen. No associations between striatal DR availability and levodopa treatment and dyskinesias were found. In advancing PD the caudate and putamen DR availability are differentially affected. Chronic exposure to treatment with dopamine agonists, but no levodopa, suppresses striatal DR availability, which may have relevance to output signaling to frontal lobes and the occurrence of executive deficits, but not dyskinesias.

摘要

我们旨在研究帕金森病(PD)患者纹状体多巴胺受体 2(DR)可用性的完整性和临床相关性。我们研究了 68 名 PD 患者,涵盖了从早期到晚期疾病阶段的患者,以及 12 名健康对照者。所有参与者在停药状态下接受一次 [C]raclopride PET 扫描,以量化纹状体 DR 可用性。使用简化参考组织模型,以小脑作为参考组织,从 [C]raclopride 动态扫描中生成 [C]raclopride 不可置换结合潜力的参数图像。对 PET 数据进行了分析,以与与疾病负担和多巴胺能治疗相关的临床数据进行相关性研究。与健康对照组相比,PD 患者的尾状核 DR 降低了 16.7%,壳核 DR 增加了 3.5%。尾状核 [C]raclopride BP 越低,PD 病程越长。与从未接受过多巴胺激动剂治疗的 PD 患者相比,接受多巴胺激动剂治疗的 PD 患者的尾状核和壳核 DR 可用性分别降低了 9.2%和 12.8%。终生多巴胺激动剂治疗量与尾状核和壳核 DR 可用性的降低相关。未发现纹状体 DR 可用性与左旋多巴治疗和运动障碍之间存在相关性。在 PD 进展过程中,尾状核和壳核的 DR 可用性受到不同的影响。慢性暴露于多巴胺激动剂治疗,但不暴露于左旋多巴治疗,会抑制纹状体 DR 可用性,这可能与额叶输出信号和执行功能缺陷的发生有关,但与运动障碍无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0758/5577411/e2acdbd32340/gr1.jpg

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