Analyses of differentially expressed genes after exposure to acute stress, acute ethanol, or a combination of both in mice.
Analyses of differentially expressed genes after exposure to acute stress, acute ethanol, or a combination of both in mice.
复制标题
暴露于急性应激，急性乙醇或两者中两者的组合后，分析差异表达的基因。
DOI：
10.1016/j.alcohol.2016.08.008
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发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
Lu L
中科院分区：
文献类型：
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作者：
Baker JA;Li J;Zhou D;Yang M;Cook MN;Jones BC;Mulligan MK;Hamre KM;Lu L
酒精滥用是一种复杂的疾病，它会受到其他因素的干扰，包括压力。在本研究中，我们研究了BXD重组近交系小鼠暴露于乙醇（NOE），应激（RSS），以及两者的组合（RSE）后海马中的基因表达。对小鼠给予腹膜内（i. p.）注射1.8g/kg乙醇或生理盐水，两组亚组或对照组暴露于急性束缚应激15 min。使用微阵列分析检测海马中的基因表达。进一步评估显著（p < 0.05，q < 0.1）差异表达的基因。生物信息学分析主要使用GeneNetwork提供的工具进行。org，包括基因本体论，顺式调节或多态性的存在，表型相关性，和主成分分析。组间差异基因表达的比较显示几乎没有重叠。基因本体证明了不同的生物学过程中，每个组与组合曝光（RSE）是唯一的乙醇（NOE）或应力（RSS）组，这表明这些变量之间的相互作用是通过不同的分子途径介导的。这支持了这样的假设，即暴露于压力改变乙醇诱导的基因表达的变化，暴露于酒精改变应激诱导的基因表达的变化。在治疗后的所有组中分析行为，并且许多差异表达的基因与实验组内的行为变化相关。有趣的是，在每组中，几个基因与相同的表型相关，这表明这些基因是重要遗传网络的潜在起源。每组内不同的差异表达基因组为识别分子网络提供了基础，这些网络可能有助于理解应激和乙醇之间复杂的相互作用，并可能提供相关的治疗靶点。使用Ptp 4a 1，一个候选基因的数量性状位点的几个这些表型，和网络分析，我们表明，一个大组的差异表达的基因在NOE组是高度相关的，其中一些先前已被链接到酒精成瘾或酒精相关的表型。
Alcohol abuse is a complex disorder, which is confounded by other factors, including stress. In the present study, we examined gene expression in the hippocampus of BXD recombinant inbred mice after exposure to ethanol (NOE), stress (RSS), and the combination of both (RSE). Mice were given an intra-peritoneal (i.p.) injection of 1.8 g/kg ethanol or saline, and subsets of both groups were exposed to acute restraint stress for 15 min or controls. Gene expression in the hippocampus was examined using microarray analysis. Genes that were significantly (p < 0.05, q < 0.1) differentially expressed were further evaluated. Bioinformatic analyses were predominantly performed using tools available at GeneNetwork. org, and included gene ontology, presence of cis-regulation or polymorphisms, phenotype correlations, and principal component analyses. Comparisons of differential gene expression between groups showed little overlap. Gene Ontology demonstrated distinct biological processes in each group with the combined exposure (RSE) being unique from either the ethanol (NOE) or stress (RSS) group, suggesting that the interaction between these variables is mediated through diverse molecular pathways. This supports the hypothesis that exposure to stress alters ethanol-induced gene expression changes and that exposure to alcohol alters stress-induced gene expression changes. Behavior was profiled in all groups following treatment, and many of the differentially expressed genes are correlated with behavioral variation within experimental groups. Interestingly, in each group several genes were correlated with the same phenotype, suggesting that these genes are the potential origins of significant genetic networks. The distinct sets of differentially expressed genes within each group provide the basis for identifying molecular networks that may aid in understanding the complex interactions between stress and ethanol, and potentially provide relevant therapeutic targets. Using Ptp4a1, a candidate gene underlying the quantitative trait locus for several of these phenotypes, and network analyses, we show that a large group of differentially expressed genes in the NOE group are highly interrelated, some of which have previously been linked to alcohol addiction or alcohol-related phenotypes.