Network preservation reveals shared and unique biological processes associated with chronic alcohol abuse in NAc and PFC.
Network preservation reveals shared and unique biological processes associated with chronic alcohol abuse in NAc and PFC.
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网络保存揭示了NAC和PFC中与慢性酒精滥用相关的共同且独特的生物学过程。
DOI：
10.1371/journal.pone.0243857
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Vladimirov VI
中科院分区：
文献类型：
--
作者：
Vornholt E;Drake J;Mamdani M;McMichael G;Taylor ZN;Bacanu SA;Miles MF;Vladimirov VI
慢性酒精滥用与中皮质边缘通路（MCL）执行功能的破坏和奖赏反应失调的调节调节有关。在这里，我们通过基因网络分析分析了酒精依赖 (AD) 匹配病例和对照 (n = 35) 的全基因组 mRNA 和 miRNA 表达，以确定前额皮质 (PFC) 和伏隔核 (NAc) 中独特和共享的失调生物过程。我们进一步研究了网络和个体基因表达水平上潜在的 mRNA/miRNA 相互作用，以确定大脑中 AD 的神经生物学机制。通过使用基因分型和估算的 SNP 数据，我们鉴定了表达数量性状位点 (eQTL)，揭示了与 AD 相关的基因网络的潜在遗传调控元件。在 Bonferroni 校正 p≤0.05 时，我们识别出显着的 mRNA（NAc = 6；PFC = 3）和 miRNA（NAc = 3；PFC = 2）AD 模块。基因集富集分析显示，PFC 和 NAc 之间保留的模块针对免疫反应过程进行富集，而参与细胞形态发生/定位和基于纤毛的细胞投射的基因仅在 NAc 模块中富集。在 Bonferroni 校正 p≤0.05 时，我们发现了显着的 mRNA/miRNA 网络模块相关性（NAc = 6；PFC = 4），这在个体转录水平上表明 miR-449a/b 作为 NAc 中细胞形态发生/定位的潜在调节因子。最后，我们确定了 eQTL（NAc：mRNA = 37，miRNA = 9；PFC：mRNA = 17，miRNA = 16），它们可能以大脑区域特异性方式介导酒精的影响。我们的研究强调了慢性酒精滥用的神经毒性作用以及可能影响酒精成瘾发展的大脑区域特定分子变化。
Chronic alcohol abuse has been linked to the disruption of executive function and allostatic conditioning of reward response dysregulation in the mesocorticolimbic pathway (MCL). Here, we analyzed genome-wide mRNA and miRNA expression from matched cases with alcohol dependence (AD) and controls (n = 35) via gene network analysis to identify unique and shared biological processes dysregulated in the prefrontal cortex (PFC) and nucleus accumbens (NAc). We further investigated potential mRNA/miRNA interactions at the network and individual gene expression levels to identify the neurobiological mechanisms underlying AD in the brain. By using genotyped and imputed SNP data, we identified expression quantitative trait loci (eQTL) uncovering potential genetic regulatory elements for gene networks associated with AD. At a Bonferroni corrected p≤0.05, we identified significant mRNA (NAc = 6; PFC = 3) and miRNA (NAc = 3; PFC = 2) AD modules. The gene-set enrichment analyses revealed modules preserved between PFC and NAc to be enriched for immune response processes, whereas genes involved in cellular morphogenesis/localization and cilia-based cell projection were enriched in NAc modules only. At a Bonferroni corrected p≤0.05, we identified significant mRNA/miRNA network module correlations (NAc = 6; PFC = 4), which at an individual transcript level implicated miR-449a/b as potential regulators for cellular morphogenesis/localization in NAc. Finally, we identified eQTLs (NAc: mRNA = 37, miRNA = 9; PFC: mRNA = 17, miRNA = 16) which potentially mediate alcohol’s effect in a brain region-specific manner. Our study highlights the neurotoxic effects of chronic alcohol abuse as well as brain region specific molecular changes that may impact the development of alcohol addiction.
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影响因子：
3.1
作者：
Ehrlich AT;Semache M;Bailly J;Wojcik S;Arefin TM;Colley C;Le Gouill C;Gross F;Lukasheva V;Hogue M;Darcq E;Harsan LA;Bouvier M;Kieffer BL
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Izaurralde, Elisa
影响因子：
3
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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