Effects of chronic morphine and morphine withdrawal on gene expression in rat peripheral blood mononuclear cells
Effects of chronic morphine and morphine withdrawal on gene expression in rat peripheral blood mononuclear cells
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DOI：
10.1016/j.neuropharm.2008.08.027
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发表时间：
2008-12-01
影响因子：
4.7
通讯作者：
Marie-Claire, Cynthia
中科院分区：
文献类型：
--
作者：
Desjardins, Stephane;Belkai, Emilie;Marie-Claire, Cynthia
慢性吗啡治疗改变了大脑结构中的基因表达。越来越多的证据表明，在心理问题中，血细胞和大脑之间的基因表达调控存在相关性。为了测试血细胞中的基因表达调控是否可以在药物成瘾中找到，我们研究了生理盐水和吗啡处理的大鼠外周血单核细胞（PBMC）中的基因表达谱。在长期用吗啡处理的大鼠中，观察自发戒断的行为体征并确定戒断评分。该评分能够选择动物表现出最轻微和最强烈戒断体征的时间点（末次注射后12 h和36 h）。使用寡核苷酸阵列评估PBMC中的差异基因表达，并使用定量实时RT-PCR验证最后一次注射后12 h和36 h几个候选基因的调节。在812个差异表达的候选者中，已经描述了几个基因（Adcy 5，Htr 2a）和途径（Map激酶，G蛋白，整合素）在吗啡处理的大鼠脑中被调节。在24个测试的候选者中，有16个在12小时时被验证，其中一些在36小时时显示出持续的调制，而对于其中的大多数，调制随着戒断评分的增加而演变。这项研究表明，在PBMCs和吗啡处理的大鼠脑的基因表达谱之间的相似性。因此，通过对血细胞的转录分析来寻找戒断严重程度与PBMCs基因表达模式之间的相关性，对于成瘾机制的研究具有重要意义。(C)2008爱思唯尔有限公司保留所有权利。
Chronic morphine treatment alters gene expression in brain structures. There are increasing evidences showing a correlation, in gene expression modulation, between blood cells and brain in psychological troubles. To test whether gene expression regulation in blood cells could be found in drug addiction, we investigated gene expression profiles in peripheral blood mononuclear (PBMC) cells of saline and morphine-treated rats. In rats chronically treated with morphine, the behavioral signs of spontaneous withdrawal were observed and a withdrawal score was determined. This score enabled to select the time points at which the animals displayed the mildest and strongest withdrawal signs (12 h and 36 h after the last injection). Oligonucleotide arrays were used to assess differential gene expression in the PBMCs and quantitative real-time RT-PCR to validate the modulation of several candidate genes 12 h and 36 h after the last injection. Among the 812 differentially expressed candidates, several genes (Adcy5, Htr2a) and pathways (Map kinases, G-proteins, integrins) have already been described as modulated in the brain of morphine-treated rats. Sixteen Out of the twenty-four tested candidates were validated at 12 h, some of them showed a Sustained modulation at 36 h while for most of them the modulation evolved as the withdrawal score increased. This study Suggests similarities between the gene expression profile in PBMCs and brain of morphine-treated rats. Thus, the searching of correlations between the severity of the withdrawal and the PBMCs gene expression pattern by transcriptional analysis of blood cells could be promising for the study of the mechanisms of addiction. (C) 2008 Elsevier Ltd. All rights reserved.