Department of Experimental and Clinical Pharmacology, University of Catania, Catania, Italy.
Neuropharmacology. 2011 May;60(6):892-900. doi: 10.1016/j.neuropharm.2011.01.026. Epub 2011 Jan 25.
Pramipexole (PPX) is a dopamine agonist with an 8-fold higher affinity for D3 than D2 receptor, whose efficacy in the treatment of Parkinson's disease is based on dopamine agonistic activity. PPX has also been recently shown to be endowed with neuroprotective activity and neurogenic potential. The aim of this study was a more detailed characterization of PPX-induced neurogenesis. Both D2 and D3 receptors are expressed in floating and differentiated neurospheres obtained from the sub-ventricular zone (SVZ) of adult mice. Treatment of secondary neurospheres with 10 μM PPX causes a marked induction of cell proliferation, assessed by enhanced cell number and S phase population at cell cycle analysis. Stimulation of proliferation by PPX is still detectable in plated neurospheres before the onset of migration and differentiation, as by enhanced BrdU incorporation. This effect is sensitive to the selective D3 dopamine receptor antagonist U99194A, as well as to sulpiride. A 24 h treatment with PPX does not modify the morphology of neurosphere-derived cells, but causes an increase of glial fibrillary acidic protein (GFAP)-positive cells, an effect sensitive to both D2 and D3 antagonism. Differentiation toward the neuronal lineage is increased by PPX as shown by enhancement of the cell population positive to the early neuronal marker doublecortin (DCX) at 24 h and the mature neuronal marker microtubule associated protein (MAP2) at 72 h. This effect is not modified by treatment with U99194A and is mimicked by BDNF. Accordingly, PPX increases BDNF release with a mechanism involving D2 but not D3 receptors.
普拉克索（PPX）是一种多巴胺激动剂，对 D3 受体的亲和力比 D2 受体高 8 倍，其在治疗帕金森病中的疗效基于多巴胺激动活性。最近还发现 PPX 具有神经保护活性和神经发生潜力。本研究的目的是更详细地描述 PPX 诱导的神经发生。D2 和 D3 受体都在成年小鼠侧脑室下区（SVZ）获得的悬浮和分化神经球中表达。用 10 μM PPX 处理二级神经球会导致细胞增殖明显增加，通过细胞周期分析评估细胞数量增加和 S 期细胞群。在迁移和分化开始之前，PPX 对增殖的刺激仍可在铺板神经球中检测到，这是通过增强 BrdU 掺入来实现的。这种效应对选择性 D3 多巴胺受体拮抗剂 U99194A 以及舒必利敏感。PPX 处理 24 小时不会改变神经球源性细胞的形态，但会导致神经胶质纤维酸性蛋白（GFAP）阳性细胞增加，这种效应对 D2 和 D3 拮抗作用均敏感。如 24 小时时早期神经元标志物双皮质素（DCX）阳性细胞群体增加以及 72 小时时成熟神经元标志物微管相关蛋白（MAP2）阳性细胞群体增加所示，PPX 可促进向神经元谱系分化。U99194A 处理不会改变这种效应，BDNF 可模拟这种效应。因此，PPX 通过涉及 D2 但不涉及 D3 受体的机制增加 BDNF 的释放。
