Profiling of methamphetamine-induced modifications of gene expression patterns in the mouse brain

Profiling of methamphetamine-induced modifications of gene expression patterns in the mouse brain
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DOI:
10.1196/annals.1316.010
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发表时间:
2004-01-01
期刊:
CURRENT STATUS OF DRUG DEPENDENCE / ABUSE STUDIES: CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY
影响因子:
--
通讯作者:
Wada, K
Wada, K
中科院分区:
其他
文献类型:
--
作者:
Funada, M;Zhou, X;Wada, K

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最近描述的DNA微阵列技术允许平行筛选表达模式和几十万个基因的调控。在本研究中,我们使用微阵列检测了在完成7天治疗期后24小时牺牲的小鼠中脑中的基因表达,该治疗期包括每天一次生理盐水(SS)治疗,生理盐水随后单次2 mg/kg体重剂量的甲基苯丙胺(S-METH),或重复2 mg/kg剂量的甲基苯丙胺(M-METH)产生致敏和位置偏好(奖励效应)。我们使用了市售的cDNA微阵列。在整个大脑中,大约80%的评估转录本达到了Affymetrix“存在”和“改变”的标准,并且在SS数据与S-METH或M-METH数据的比较中显示杂交强度差异值大于或等于1.5倍。S-METH基因表达变化为上调和下调,其中13个转录本上调,13个转录本下调,而M-METH基因表达变化以下调为主,其中5个转录本上调,21个转录本下调。我们确定了在S-METH和M-METH组中改变表达的几个基因:转录因子基因、细胞应激/分子伴侣基因和细胞调节基因。
Recently described DNA microarray technology allows parallel screening of expression patterns and regulation of hundreds of thousands of genes. In the present study, we used a microarray to examine the gene expressions in the midbrains of mice sacrificed 24 h after completion of a 7-day treatment period consisting of a once-daily treatment with saline (SS), saline followed by a single 2 mg/kg of body weight dose of methamphetamine (METH) (S-METH), or repeated 2 mg/kg METH doses (M-METH) that produced sensitization and place preference (rewarding effect). We used the commercially available cDNA microarray. Approximately 80 % of the assessed transcripts in the total brain reached the Affymetrix criteria for "present" and "changed," as well as displaying greater than or equal to 1.5-fold differences in hybridization intensity difference values in a comparison of SS data to S-METH or M-METH data. S-METH gene expression changes were observed in both up- and downregulation, with 13 transcripts upregulated and 13 downregulated, whereas the majority of M-METH gene expression changes were observed in downregulation, with 5 transcripts upregulated and 21 downregulated. We identified several genes that altered expression in both the S-METH and M-METH groups: a transcription factor gene, cellular stress/molecular chaperones, and a cellular regulatory gene.