Decreased binding of the D3 dopamine receptor-preferring ligand [11C]-()-PHNO in drug-nave Parkinsons disease
Decreased binding of the D3 dopamine receptor-preferring ligand [11C]-()-PHNO in drug-nave Parkinsons disease
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DOI：
10.1093/brain/awn337
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发表时间：
2009-05-01
期刊：
影响因子：
14.5
通讯作者：
Kish, Stephen J.
中科院分区：
文献类型：
--
作者：
Boileau, Isabelle;Guttman, Mark;Kish, Stephen J.
D-3多巴胺（DA）受体是D-2样DA受体家族的成员。虽然D-2受体是丰富的，特别是在运动区的纹状体，D-3受体显示出相对丰富的边缘区和苍白球。这种受体目前在神经病学中引起关注，因为它可能参与帕金森病的精神和运动并发症，以及多巴胺D-3-偏好激动剂治疗可能延迟疾病进展的可能性。临床前数据表明，黑质纹状体DA神经元损伤后，D-3（而不是D-2）DA受体的纹状体水平降低;目前，在帕金森病中没有关于该受体亚型的体内数据。这项正电子发射断层扫描研究的目的是比较非抑郁、非痴呆、多巴胺能药物初治的早期帕金森病患者（n 10）与匹配对照组（n 9）脑中[C-11]-（）-PHNO（D-3与D-2偏好）和[C-11]雷氯必利（D-3 D-2）的结合。帕金森病与富含D-3的腹侧纹状体中[C-11]-（）-PHNO（而非[C-11]雷氯必利）结合双侧降低的趋势相关（11，P 0.07），苍白球中的结合显著降低（42，P 0.02）。相比之下，在主要为D-2的壳核中，[C-11]-（）-PHNO（25，P 0.02）和[C-11]雷氯必利（25，P 0.01）结合率均相似地增加，尤其是在症状对侧。在中脑中，可能含有定位于黑质的D-3受体，[C-11]-（）-PHNO结合正常。[C-11]-（）-PHNO与[C-11]雷氯必利比值降低与运动缺陷和情绪低落相关（P 0.02）。我们的成像数据表明，在人类大脑DA神经元的损失导致DA的D-2和D-3受体的区域特异性差异变化与D-3受体下调可能与帕金森病的一些运动和情绪问题。D-3受体水平可能是与治疗相关的副作用的决定性脆弱性因素;因此，这些初步发现提供了有价值的基线信息，以了解D-3受体在帕金森病药物治疗中的作用。
The D-3 dopamine (DA) receptor is a member of the D-2-like DA receptor family. While the D-2 receptor is abundant especially in motor-regions of the striatum, the D-3 receptor shows a relative abundance in limbic regions and globus pallidus. This receptor is of current interest in neurology because of its potential involvement in psychiatric and motor complications in Parkinsons disease and the possibility that dopamine D-3-preferring agonist therapy might delay progression of the disorder. Preclinical data indicate that striatal levels of the D-3 (but not the D-2) DA receptor are decreased following lesion of nigrostriatal DA neurons; at present, there are no in vivo data on this receptor subtype in Parkinsons disease. The objective of this positron emission tomography study was to compare [C-11]-()-PHNO (D-3 versus D-2 preferring) and [C-11]raclopride (D-3 D-2) binding in brain of non-depressed, non-demented, dopaminergic drug-nave patients with early-stage Parkinsons disease (n 10), relative to matched-controls (n 9). Parkinsons disease was associated with a trend for bilaterally decreased [C-11]-()-PHNO (but not [C-11]raclopride) binding in the D-3-rich ventral striatum (11, P 0.07) and significantly decreased binding in globus pallidus (42, P 0.02). In contrast, in the primarily D-2-populated putamen, both [C-11]-()-PHNO (25, P 0.02) and [C-11]raclopride (25, P 0.01) binding were similarly increased, especially on the side contra-lateral to the symptoms. In the midbrain, presumably containing D-3 receptors localized to the substantia nigra, [C-11]-()-PHNO binding was normal. Decreased [C-11]-()-PHNO to [C-11]raclopride ratio correlated with motor deficits and lowered-mood (P 0.02). Our imaging data suggest that brain DA neuron loss in the human causes region-specific differential changes in DA D-2 and D-3 receptors with D-3 receptor downregulation possibly related to some motor and mood problems in Parkinson disease. D-3 receptor levels might be a determinant vulnerability factor underlying side-effects associated with treatment; hence, these initial findings provide valuable baseline information to understand the role of D-3 receptors in response to Parkinsons disease medication.