cDNA Array Analysis of Cu/Zn SOD Tg Mice Treated with Neurotoxic Doses of AMPH

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末梢变性。超氧化物自由基似乎参与了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）小鼠中被减弱。为了详细分析与AMPH毒性相关的分子变化，我们使用由1176个基因组成的cDNA阵列来检测野生型和SOD-tg小鼠在神经毒性剂量下纹状体中基因表达的差异变化。在研究过程中，我们发现42个基因在至少两个连续的时间点上表现出bbbb1.8倍的变化，并且在两种基因型中受到AMPH的不同影响。有几个基因显示出与超氧化物相关的变化。我们正在描述AMPH对大脑皮层基因表达的影响。

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. Several genes showed changes that were superoxide-dependent. We are characterizing the effects of AMPH on gene expression in the cortex.