The dissection of transcriptional modules regulated by various drugs of abuse in the mouse striatum.
The dissection of transcriptional modules regulated by various drugs of abuse in the mouse striatum.
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DOI：
10.1186/gb-2010-11-5-r48
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发表时间：
2010
期刊：
影响因子：
12.3
通讯作者：
Przewlocki R
中科院分区：
文献类型：
--
作者：
Piechota M;Korostynski M;Solecki W;Gieryk A;Slezak M;Bilecki W;Ziolkowska B;Kostrzewa E;Cymerman I;Swiech L;Jaworski J;Przewlocki R
在小鼠大脑中评估了对六种常见滥用药物的转录反应，揭示了药物诱导基因的共同模块。滥用各种药物会激活大脑奖赏系统中的细胞内通路。这些途径调节对成瘾发展至关重要的基因的表达。为了揭示不同类型药物滥用的共同和独特基因，我们比较了尼古丁、乙醇、可卡因、吗啡、海洛因和甲基苯丙胺对小鼠纹状体基因表达谱的影响。我们应用全基因组微阵列分析来评估小鼠急性给药后转录组改变的详细时间过程（1,2,4和8小时）。我们鉴定了42个药物反应基因，这些基因被分离成两个主要的转录模块。第一个模块包括由精神兴奋剂和阿片类药物诱导的活性依赖性转录本（包括Fos和Npas4）。第二组基因（包括Fkbp5和S3-12）部分受类固醇激素的释放控制，被乙醇和阿片类药物强烈激活。使用药理学工具，我们能够抑制药物相关基因组谱的特定模块的诱导。我们选择了一个基因子集进行原位杂交和定量PCR验证。我们还发现，敲低药物反应基因Sgk1和Tsc22d3会导致小鼠树突棘的改变，这可能反映了可塑性改变的潜力。我们的研究确定了药物诱导基因的模块共享功能关系。这些基因可能在成瘾的早期阶段起着关键作用。
The transcriptional response to six commonly-abused drugs was assessed in the mouse brain revealing common modules of drug-induced genes. Various drugs of abuse activate intracellular pathways in the brain reward system. These pathways regulate the expression of genes that are essential to the development of addiction. To reveal genes common and distinct for different classes of drugs of abuse, we compared the effects of nicotine, ethanol, cocaine, morphine, heroin and methamphetamine on gene expression profiles in the mouse striatum. We applied whole-genome microarray profiling to evaluate detailed time-courses (1, 2, 4 and 8 hours) of transcriptome alterations following acute drug administration in mice. We identified 42 drug-responsive genes that were segregated into two main transcriptional modules. The first module consisted of activity-dependent transcripts (including Fos and Npas4), which are induced by psychostimulants and opioids. The second group of genes (including Fkbp5 and S3-12), which are controlled, in part, by the release of steroid hormones, was strongly activated by ethanol and opioids. Using pharmacological tools, we were able to inhibit the induction of particular modules of drug-related genomic profiles. We selected a subset of genes for validation by in situ hybridization and quantitative PCR. We also showed that knockdown of the drug-responsive genes Sgk1 and Tsc22d3 resulted in alterations to dendritic spines in mice, possibly reflecting an altered potential for plastic changes. Our study identified modules of drug-induced genes that share functional relationships. These genes may play a critical role in the early stages of addiction.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
16.2
作者：
Chowdhury, Shoaib;Shepherd, Jason D.;Worley, Paul F.
通讯作者：
Worley, Paul F.
影响因子：
4.5
作者：
Choy E;Yelensky R;Bonakdar S;Plenge RM;Saxena R;De Jager PL;Shaw SY;Wolfish CS;Slavik JM;Cotsapas C;Rivas M;Dermitzakis ET;Cahir-McFarland E;Kieff E;Hafler D;Daly MJ;Altshuler D
通讯作者：
Altshuler D
影响因子：
4.4
作者：
Chipkin, SR;van Bueren, A;McCall, AL
通讯作者：
McCall, AL
影响因子：
5.3
作者：
David, S;Stegenga, SL;Kalb, RG
通讯作者：
Kalb, RG