Early and late gene changes in MPTP mice model of Parkinson's disease employing cDNA microarray
Early and late gene changes in MPTP mice model of Parkinson's disease employing cDNA microarray
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DOI：
10.1023/a:1020989812576
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发表时间：
2002-10-01
影响因子：
4.4
通讯作者：
Youdim, MBH
中科院分区：
文献类型：
--
作者：
Mundel, S;Grünblatt, E;Youdim, MBH
最近，我们报道了在慢性MPTP模型中，在变性的晚期，采用cDNA表达阵列，这表明参与神经元细胞死亡的事件的“多米诺骨牌”级联的特定脑基因表达的变化。为了阐明急性MPTP处理小鼠（3-24 h）黑质（SN）和纹状体区域的早期基因表达谱，我们选择了受长期MPTP处理影响的有限数量的基因，并检查了它们的表达。具体来说，我们检测到氧化应激、炎症过程、信号转导和谷氨酸毒性相关基因表达的改变。这些前毒性基因似乎通过营养因子和抗氧化防御的表达升高来补偿，这些营养因子和抗氧化防御也通过短时间暴露于MPTP而被激活。这些基因表达变化的时间过程表明，调查早期基因级联事件发生之前，晚黑质纹状体多巴胺神经元细胞死亡的重要性。
Recently, we reported specific brain gene expression changes in the chronic MPTP model in the late stage of degeneration, employing cDNA expression array, which indicate a "domino" cascade of events involved in neuronal cell death. In an attempt to elucidate early gene expression profile in the region of the substantia nigra (SN) and the striatum of acute MPTP-treated mice (3-24 h), we elected a restricted number of genes affected by the long-term MPTP treatment, and their expression was examined. Specifically, we detected alterations in the expression of genes implicated in oxidative-stress, inflammatory processes, signal transduction and glutamate toxicity. These pro-toxic genes appear to be compensated by the elevated expression in trophic factors and antioxidant defenses, which are also activated by short exposure to MPTP. The time course of these gene expression changes indicates the importance of investigating the early gene cascade of events occurring prior to late nigrostriatal dopamine neuronal cell death.