S100B Transgenic Mice Develop Features of Parkinson's Disease
S100B Transgenic Mice Develop Features of Parkinson's Disease
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DOI：
10.1016/j.arcmed.2011.01.005
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发表时间：
2011-01-01
影响因子：
7.7
通讯作者：
Qin, Chuan
中科院分区：
文献类型：
--
作者：
Liu, Jialin;Wang, Hailin;Qin, Chuan
背景和目的。帕金森病（PD）是最常见的神经退行性疾病之一。到目前为止，PD的病因和机制尚不清楚，需要进一步的研究。本研究旨在建立脑特异性S100B基因转基因小鼠，探讨S100B在pd发生中的作用。通过将人S100B基因下游插入血小板衍生生长因子（PDGF）启动子构建hS100B转基因载体，并进行微注射制备转基因小鼠。采用Rota-rod法测定S100B转基因组（TG）、S100B基因敲除组（KG）和非转基因对照组（CG）小鼠的运动协调能力。采用RT-PCR、Western blotting检测大鼠脑组织中多巴胺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，以及中脑组织中二氧苯丙氨酸（DOPA）、多巴胺（DA）、同型香兰酸（HVA）、5-羟色胺（5-HT）、5-羟基吲哚乙酸（5-HIAA）的水平。高效液相色谱-荧光检测法（HPLC-FLD）。与CG相比，TG中小鼠运动协调能力、D2DR、GRK2表达、5-HT水平明显降低，多巴、DA及其代谢产物HVA水平升高，D1DR、GRK5、TH、5-HIAA表达相似。与CG比较，kg组各项检测指标无明显变化。S100B在脑内过表达导致运动协调障碍，这可能与D2DR和GRK2表达下调、DA合成和代谢增加、5-HT水平降低有关。因此，S100B可能是PD发病的一个潜在原因。(C) 2011 IMSS。Elsevier Inc.出版。
Background and Aims. 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.Methods. 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.Results. 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.Conclusions. 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. (C)2011 IMSS. Published by Elsevier Inc.