Chronic intermittent ethanol exposure and its removal induce a different miRNA expression pattern in primary cortical neuronal cultures.
Chronic intermittent ethanol exposure and its removal induce a different miRNA expression pattern in primary cortical neuronal cultures.
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DOI：
10.1111/j.1530-0277.2011.01689.x
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发表时间：
2012-06
期刊：
影响因子：
--
通讯作者：
Qiang M
中科院分区：
文献类型：
--
作者：
Guo Y;Chen Y;Carreon S;Qiang M
越来越多的证据表明，反复接触酒精和戒酒会导致持久的分子和细胞适应。发生的一种分子适应是基因表达的调节，这被认为会导致成瘾特征的功能改变：耐受性，依赖性，戒断，渴望和复发。microRNA（miRNAs）是近年来发现的通过转录后调节基因表达的主要调控因子。然而，miRNAs在酒精去除后的神经适应中的作用尚未得到直接解决。我们采用慢性间歇性乙醇（CIE）模型在原代皮层神经元培养，以检查使用TaqMan实时PCR miRNA阵列的差异miRNA表达的全球范围。与未处理的对照值相比，在CIE（CIE10）处理10天后（n = 42，FDR < 0.05 and fold change >2）和CIE（P5）处理后5天（n = 26），62种miRNA差异表达。与CIE 10相比，P5中的乙醇去除经验诱导了不同的表达模式，包括20种差异表达的miRNA，其在CIE 10下未表现出显著变化。乙醇去除诱导的miRNAs的预测靶分子主要在基因转录的调节中起作用，但也在神经元分化、胚胎发育、蛋白磷酸化和突触可塑性中起作用。有趣的是，CIE处理后5天差异表达的一些miRNA被发现聚集在CpG岛附近的染色体上，表明它们通过靶向酒精相关基因而具有功能相似性。总之，这些结果表明差异表达的miRNA在介导乙醇去除相关表型中的潜在作用。
Increasing evidence indicates that repeated exposure to and withdrawal from alcohol can result in persistent molecular and cellular adaptations. One molecular adaptation that occurs is the regulation of gene expression, which is thought to lead to the functional alterations that characterize addiction: tolerance, dependence, withdrawal, craving, and relapse. MicroRNAs (miRNAs) have been recently identified as master regulators of gene expression through post-transcriptional regulation. However, the role of miRNAs in the neuroadaptations after alcohol removal has not yet been directly addressed. We employed a chronic intermittent ethanol (CIE) model in primary cortical neuronal cultures to examine the global extent of differential miRNA expression using a TaqMan real-time PCR miRNA array. Sixty-two miRNAs were differentially expressed after 10 days of CIE (CIE10) treatment (n = 42 with FDR < 0.05 and fold change > 2) and 5 days post-CIE (P5) treatment (n = 26) compared to untreated control values. Compared to CIE10, ethanol removal experience in P5 induced a distinct expression pattern, including 20 differentially expressed miRNAs, which did not exhibit a significant change at CIE10. The predicted target molecules of ethanol removal-induced miRNAs function mainly in the regulation of gene transcription, but also function in neuron differentiation, embryonic development, protein phosphorylation, and synaptic plasticity. Interestingly, some of the miRNAs differentially expressed 5 days after CIE treatment were found to cluster on chromosomes near CpG islands, suggesting that they share functional similarity by targeting alcohol-related genes. Taken together, these results suggest a potential role of differentially expressed miRNAs in mediating ethanol removal-related phenotypes.
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影响因子：
25
作者：
Im, Heh-In;Hollander, Jonathan A.;Bali, Purva;Kenny, Paul J.
通讯作者：
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影响因子：
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大脑表达的microRNA与精神分裂症病因有关。
影响因子：
3.7
作者：
Hansen, Thomas;Olsen, Line;Lindow, Morten;Jakobsen, Klaus D.;Ullum, Henrik;Jonsson, Erik;Andreassen, Ole A.;Djurovic, Srdjan;Melle, Ingrid;Agartz, Ingrid;Hall, Hakan;Timm, Sally;Wang, August G.;Werge, Thomas
通讯作者：
Werge, Thomas
影响因子：
10.6
作者：
Huang, Weihua;Li, Ming D.
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