Morphine effects on striatal transcriptome in mice.
Morphine effects on striatal transcriptome in mice.
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DOI：
10.1186/gb-2007-8-6-r128
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发表时间：
2007
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：
Korostynski M;Piechota M;Kaminska D;Solecki W;Przewlocki R
急性和慢性暴露于吗啡后小鼠纹状体的全球转录分析揭示了多种可能影响阿片样物质相关表型的生理因素，并涉及一些基因网络，包括糖皮质激素受体调节基因，在对这种阿片样物质的反应中。长期使用阿片类药物会在神经系统中产生分子和细胞适应性，导致耐受性、身体依赖性和成瘾性。全基因组比较吗啡诱导的具有不同阿片类药物相关表型的小鼠品系的脑转录变化，为发现基因表达与对药物的行为反应之间的关系提供了机会。在这里，我们分析了单次和重复吗啡给药在选定的近交系小鼠品系（129 P3/J，DBA/2 J，C57 BL/6 J，和SWR/J）的影响。使用基于微阵列的纹状体基因表达谱，我们发现了618个（错误发现率< 1%）吗啡反应转录本。通过本体分类，我们将特定的基因组与生物功能联系起来，包括新陈代谢，神经冲动的传递和细胞间信号传导。我们发现了许多新的吗啡调节基因（例如Olig 2和Camk 1g），以及许多具有菌株特异性表达变化的转录本（例如Hspa 1a和Fzd 2）。此外，共表达基因（例如，Tsc 22 d3和Nfkbia）模式的转录激活被鉴定为通过糖皮质激素受体（GR）介导。进一步的研究表明，GR的阻断改变了吗啡诱导的自发活动和身体依赖性的发展。我们的研究结果表明，有不同的菌株之间的转录响应急性吗啡治疗的幅度和慢性吗啡治疗后观察到的基因表达的耐受程度。使用纹状体中吗啡效应的全基因组转录分析，我们能够揭示可能影响阿片类药物相关表型的多种生理因素，并将特定基因网络与这一复杂性状联系起来。研究结果还表明，GR调节基因可能参与介导吗啡的行为反应。
Global transcriptional analysis of mouse striata following acute and chronic exposure to morphine reveals multiple physiological factors which may affect opioid-related phenotypes and implicates a number of gene networks, including glucocorticoid receptor regulated genes, in the response to this opioid. Chronic opiate use produces molecular and cellular adaptations in the nervous system that lead to tolerance, physical dependence, and addiction. Genome-wide comparison of morphine-induced changes in brain transcription of mouse strains with different opioid-related phenotypes provides an opportunity to discover the relationship between gene expression and behavioral response to the drug. Here, we analyzed the effects of single and repeated morphine administrations in selected inbred mouse strains (129P3/J, DBA/2J, C57BL/6J, and SWR/J). Using microarray-based gene expression profiling in striatum, we found 618 (false discovery rate < 1%) morphine-responsive transcripts. Through ontologic classification, we linked particular sets of genes to biologic functions, including metabolism, transmission of nerve impulse, and cell-cell signaling. We identified numerous novel morphine-regulated genes (for instance, Olig2 and Camk1g), and a number of transcripts with strain-specific changes in expression (for instance, Hspa1a and Fzd2). Moreover, transcriptional activation of a pattern of co-expressed genes (for instance, Tsc22d3 and Nfkbia) was identified as being mediated via the glucocorticoid receptor (GR). Further studies revealed that blockade of the GR altered morphine-induced locomotor activity and development of physical dependence. Our results indicate that there are differences between strains in the magnitude of transcriptional response to acute morphine treatment and in the degree of tolerance in gene expression observed after chronic morphine treatment. Using whole-genome transcriptional analysis of morphine effects in the striatum, we were able to reveal multiple physiological factors that may influence opioid-related phenotypes and to relate particular gene networks to this complex trait. The results also suggest the possible involvement of GR-regulated genes in mediating behavioral response to morphine.
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DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
DNA变异和脑区域特异性表达谱图在近交小鼠菌株之间表现出不同的关系：对EQTL映射研究的影响。
影响因子：
12.3
作者：
Hovatta, Iiris;Zapala, Matthew A.;Broide, Ron S.;Schadt, Eric E.;Libiger, Ondrej;Schork, Nicholas J.;Lockhart, David J.;Barlow, Carrolee
通讯作者：
Barlow, Carrolee
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：
4.7
作者：
Bailey, A;Davis, L;Kitchen, I
通讯作者：
Kitchen, I
影响因子：
30.8
作者：
Chesler, EJ;Lu, L;Williams, RW
通讯作者：
Williams, RW