Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Comparative Medical Center, Peking Union Medical College, Panjiayuan No. 5, Chaoyang, Beijing, P.R. China.
Arch Med Res. 2011 Jan;42(1):1-7. doi: 10.1016/j.arcmed.2011.01.005.
Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Until now, the cause and mechanism of PD are unknown, making further studies necessary. We undertook this study to establish the brain-specific S100B gene transgenic mice and investigate the role of S100B in the development of PD.
The hS100B transgenic vector was constructed by inserting the human S100B gene downstream into platelet-derived growth factor (PDGF) promoter, followed by microinjection to produce transgenic mice. Motor coordination ability of mice in the S100B transgenic group (TG), S100B knockout group (KG) and the non-transgenic control group (CG) were measured by the Rota-rod test. The expressions of dopamine D1 receptor (D1DR), dopamine D2 receptor (D2DR), G protein-coupled receptor kinase2 (GRK2), G protein-coupled receptor kinase5 (GRK5), tyrosine hydroxylase (TH) in the brain tissue, and levels of dioxyphenylalanine (DOPA), dopamine (DA), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the midbrain tissue were detected by RT-PCR, Western blotting, and high-performance liquid chromatography-fluorescence detection method (HPLC-FLD), respectively.
Compared with CG, in TG, the motor coordination ability of mice, expressions of D2DR and GRK2, and the level of 5-HT visibly decreased, while the levels of DOPA, DA and its metabolic product HVA increased, the expressions of D1DR, GRK5, TH and 5-HIAA were similar. Compared with CG, no obvious change of detection indexes was observed in KG.
Overexpression of S100B in the brain resulted in motor coordination impairment, which may have resulted from the downregulation of D2DR and GRK2 expressions, increased DA synthesis and metabolism, and decreased 5-HT level. Therefore, S100B may be a potential cause of pathogenesis in PD.
帕金森病（PD）是最常见的神经退行性疾病之一。迄今为止，PD 的病因和发病机制尚不清楚，因此需要进一步研究。我们进行这项研究旨在建立脑特异性 S100B 基因转基因小鼠，并探讨 S100B 在 PD 发病机制中的作用。
通过将人 S100B 基因插入血小板衍生生长因子（PDGF）启动子下游构建 hS100B 转基因载体，然后进行微注射以产生转基因小鼠。通过转棒试验测量 S100B 转基因组（TG）、S100B 敲除组（KG）和非转基因对照组（CG）中小鼠的运动协调能力。通过 RT-PCR、Western blot 和高效液相色谱-荧光检测法（HPLC-FLD）分别检测脑组织中多巴胺 D1 受体（D1DR）、多巴胺 D2 受体（D2DR）、G 蛋白偶联受体激酶 2（GRK2）、G 蛋白偶联受体激酶 5（GRK5）、酪氨酸羟化酶（TH）的表达以及中脑组织中二羟苯丙氨酸（DOPA）、多巴胺（DA）、高香草酸（HVA）、5-羟色胺（5-HT）和 5-羟吲哚乙酸（5-HIAA）的水平。
与 CG 相比，在 TG 中，小鼠的运动协调能力、D2DR 和 GRK2 的表达以及 5-HT 的水平明显降低，而 DOPA、DA 及其代谢产物 HVA 的水平升高，D1DR、GRK5、TH 和 5-HIAA 的表达相似。与 CG 相比，KG 中未观察到检测指标的明显变化。
脑内 S100B 的过度表达导致运动协调障碍，这可能是由于 D2DR 和 GRK2 表达下调、DA 合成和代谢增加以及 5-HT 水平降低所致。因此，S100B 可能是 PD 发病机制中的一个潜在病因。
