cDNA Array Analysis of Cu/Zn SOD Tg Mice Treated with Ne

安非他明（AMPH）是一种滥用药物，可导致哺乳动物纹状体多巴胺终末变性。超氧化物自由基似乎参与AMPH诱导的损伤，因为其毒性在Cu/Zn超氧化物歧化酶转基因（SOD-tg）小鼠中减弱。为了提供与AMPH毒性相关的分子变化的详细分析，我们使用由1176个基因组成的cDNA阵列来检测用神经毒性剂量的药物治疗的野生型和SOD-tg小鼠纹状体中基因表达的差异变化。我们发现42个基因在研究过程中至少连续两个时间点显示出>1.8倍的变化，并且在两种基因型中受到AMPH的不同影响。具体来说，更多的转录因子和基因参与响应损伤/炎症的影响后，野生型小鼠AMPH管理。这些刺激诱导的基因表达的超氧化物依赖性改变中的一些可能影响神经元功能并促进神经元损伤。其他变化可能有助于提供某种程度的保护，防止AMPH毒性。这些结果支持这样的观点，即使用基因表达的全球阵列分析将有助于确定新的分子介质的AMPH诱导的神经退行性变。

Amphetamine (AMPH) is a drug of abuse that causes the degeneration of striatal dopamine terminals in mammals. Superoxide radicals seem to participate in AMPH-induced damage because its toxicity is attenuated in Cu/Zn superoxide dismutase transgenic (SOD-tg) mice. To provide a detailed analysis of molecular changes associated with AMPH toxicity, we used cDNA arrays consisting of 1176 genes to detect differential changes in gene expression in the striata of wild-type and SOD-tg mice treated with neurotoxic doses of the drug. We found 42 genes that showed >1.8-fold changes in at least two consecutive time points during the course of the study and were differentially affected by AMPH in the two genotypes. Specifically, more transcription factors and genes involved in responses to injury/inflammation were affected in wild-type mice after AMPH administration. Some of these stimulant-induced superoxide-dependent alterations in gene expression might affect neuronal functions and promote neuronal damage. Other changes might help to provide some degree of protection against AMPH toxicity. These results support the view that the use of global array analysis of gene expression will help to identify novel molecular mediators of AMPH-induced neurodegeneration.