Comprehensive expression analysis of a rat depression model

Comprehensive expression analysis of a rat depression model
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DOI:
10.1038/sj.tpj.6500234
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发表时间:
2004-04
期刊:
The Pharmacogenomics Journal
影响因子:
--
通讯作者:
Noriaki Nakatani;Hiroyuki Aburatani;Hiroyuki Aburatani;Kunihiro Nishimura;Jun'ichi Semba;Takeo Yoshikawa
Noriaki Nakatani;Hiroyuki Aburatani;Hiroyuki Aburatani;Kunihiro Nishimura;Jun'ichi Semba;Takeo Yoshikawa
中科院分区:
其他
文献类型:
--
作者:
Noriaki Nakatani;Hiroyuki Aburatani;Hiroyuki Aburatani;Kunihiro Nishimura;Jun'ichi Semba;Takeo Yoshikawa

文献摘要

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在这里,我们报告了一项使用DNA微阵列对人类抑郁的“获得性无助”(LH)大鼠模型中的基因表达的大规模分析。我们比较了未经处理的对照组和用生理盐水(黄体生成素-S)、丙咪嗪或氟西汀治疗的黄体生成素大鼠额叶皮质(FC)和海马区(HPC)的基因表达。在对照组和黄体生成素-S组中,分别有34和48个转录本在Fc和HPC中差异表达。出乎意料的是,只有NADH脱氢酶和锌转运蛋白的基因在FC和HPC中都发生了改变,这表明大脑特定区域的分子过程重叠有限。主成分分析表明,FC中上调的代谢酶基因和HPC中下调的信号转导基因可以清楚地区分抑郁和对照动物,并解释对抗抑郁药物的反应。这些全面的数据可能有助于解开与人类抑郁症有关的复杂遗传倾向。
Herein we report on a large-scale analysis of gene expression in the ‘learned helplessness’(LH) rat model of human depression, using DNA microarrays. We compared gene expression in the frontal cortex (FC) and hippocampus (HPC) of untreated controls, and LH rats treated with saline (LH-S), imipramine or fluoxetine. A total of 34 and 48 transcripts were differentially expressed in the FC and HPC, respectively, between control and LH-S groups. Unexpectedly, only genes for NADH dehydrogenase and zinc transporter were altered in both the FC and HPC, suggesting limited overlap in the molecular processes from specific areas of the brain. Principal component analysis revealed that sets of upregulated metabolic enzyme genes in the FC and downregulated genes for signal transduction in the HPC can distinguish clearly between depressed and control animals, as well as explain the responsiveness to antidepressants. This comprehensive data could help to unravel the complex genetic predispositions involved in human depression.