Ho Gideon, Zhang Chunyan, Zhuo Lang
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, the Nanos, #04-01, 138669, Singapore.
Toxicol Appl Pharmacol. 2007 May 15;221(1):76-85. doi: 10.1016/j.taap.2007.01.023. Epub 2007 Feb 9.
Gliosis is a universal response of the brain to almost all types of neural insults, including neurotoxicity, neurodegeneration, viral infection, and stroke. A hallmark of gliotic reaction is the up-regulation of the astrocytic biomarker GFAP (glial fibrillary acidic protein), which often precedes the anatomically apparent damages in the brain. In this study, neonatal transgenic mice at postnatal day (PD) 4 expressing GFP (green fluorescent protein) under the control of a widely used 2.2-kb human GFAP promoter in the brain are treated with two model neurotoxicants, 1-methyl-4(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH(3)-MPTP), and kainic acid (KA), respectively, to induce gliosis. Here we show that the neurotoxicant-induced acute gliosis can be non-invasively imaged and quantified in the brain of conscious (un-anesthetized) mice in real-time, at 0, 2, 4, 6, and 8 h post-toxicant dosing. Therefore the current methodology could be a useful tool for studying the developmental aspects of neuropathies and neurotoxicity.
胶质增生是大脑对几乎所有类型神经损伤的普遍反应，包括神经毒性、神经退行性变、病毒感染和中风。胶质反应的一个标志是星形胶质细胞生物标志物GFAP（胶质纤维酸性蛋白）的上调，这通常在大脑出现明显解剖学损伤之前发生。在本研究中，分别用两种模型神经毒物1-甲基-4（2'-甲基苯基）-1,2,3,6-四氢吡啶（2'-CH(3)-MPTP）和海藻酸（KA）处理出生后第4天（PD4）在大脑中广泛使用的2.2 kb人GFAP启动子控制下表达绿色荧光蛋白（GFP）的新生转基因小鼠，以诱导胶质增生。在这里，我们表明，在给予神经毒物后的0、2、4、6和8小时，可以在清醒（未麻醉）小鼠的大脑中对神经毒物诱导的急性胶质增生进行实时无创成像和定量分析。因此，目前的方法可能是研究神经病变和神经毒性发育方面的有用工具。
