Exploration of alcohol use disorder-associated brain miRNA-mRNA regulatory networks.
Exploration of alcohol use disorder-associated brain miRNA-mRNA regulatory networks.
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DOI：
10.1038/s41398-021-01635-w
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发表时间：
2021-10-02
影响因子：
6.8
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Lim Y;Beane-Ebel JE;Tanaka Y;Ning B;Husted CR;Henderson DC;Xiang Y;Park IH;Farrer LA;Zhang H
特定大脑区域的转录组变化可能会影响酒精使用障碍（AUD）的风险，但其潜在机制尚不完全清楚。我们通过分析两组死后脑组织样本和乙醇暴露的人胚胎干细胞 (hESC) 衍生的皮质中间神经元的转录组变化，研究了多个脑区域中与 AUD 相关的 miRNA-mRNA 调控网络。对来自 12 名澳大利亚人和 12 名对照欧洲澳大利亚人的 8 个脑区（杏仁核、尾状核、小脑、海马、伏核、前额皮质、壳核和腹侧被盖区）的 192 个组织样本（第 1 组）中的 miRNA 和 mRNA 转录组进行了分析。在 AUD 受试者的一个或多个脑区中鉴定出 19 个差异表达的 miRNA（倍数变化>2.0 & P<0.05）和 97 个差异表达的 mRNA（倍数变化>2.0 & P<0.001）。使用差异表达和负相关的 miRNA-mRNA 对构建每个大脑区域中与 AUD 相关的 miRNA-mRNA 调控网络。 AUD 相关通路（包括 CREB 信号传导、IL-8 信号传导和轴突引导信号传导）可能受到 AUD 相关大脑 miRNA-mRNA 对的调节。此外，在另外 96 个组织样本（第 2 组）中绘制了 miRNA 和 mRNA 转录组图谱，这些样本来自 8 个 AUD 和 8 个对照欧洲澳大利亚人的上述 8 个大脑区域中的 6 个。一些与 AUD 相关的 miRNA-mRNA 调控网络得到了证实。此外，在暴露或不暴露乙醇的情况下，对 hESC 衍生的皮质中间神经元中的 miRNA 和 mRNA 转录组进行了分析，并构建了乙醇影响的 miRNA-mRNA 调控网络。这项研究提供的证据表明，酒精可以诱导奖赏相关或酒精反应大脑区域的 miRNA 和 mRNA 表达发生一致变化。我们得出的结论是，大脑 miRNA-mRNA 调控网络的改变可能有助于 AUD 的发展。
Transcriptomic changes in specific brain regions can influence the risk of alcohol use disorder (AUD), but the underlying mechanism is not fully understood. We investigated AUD-associated miRNA–mRNA regulatory networks in multiple brain regions by analyzing transcriptomic changes in two sets of postmortem brain tissue samples and ethanol-exposed human embryonic stem cell (hESC)-derived cortical interneurons. miRNA and mRNA transcriptomes were profiled in 192 tissue samples (Set 1) from eight brain regions (amygdala, caudate nucleus, cerebellum, hippocampus, nucleus accumbens, prefrontal cortex, putamen, and ventral tegmental area) of 12 AUD and 12 control European Australians. Nineteen differentially expressed miRNAs (fold-change>2.0 & P < 0.05) and 97 differentially expressed mRNAs (fold-change>2.0 & P < 0.001) were identified in one or multiple brain regions of AUD subjects. AUD-associated miRNA–mRNA regulatory networks in each brain region were constructed using differentially expressed and negatively correlated miRNA–mRNA pairs. AUD-relevant pathways (including CREB Signaling, IL-8 Signaling, and Axonal Guidance Signaling) were potentially regulated by AUD-associated brain miRNA–mRNA pairs. Moreover, miRNA and mRNA transcriptomes were mapped in additional 96 tissue samples (Set 2) from six of the above eight brain regions of eight AUD and eight control European Australians. Some of the AUD-associated miRNA–mRNA regulatory networks were confirmed. In addition, miRNA and mRNA transcriptomes were analyzed in hESC-derived cortical interneurons with or without ethanol exposure, and ethanol-influenced miRNA–mRNA regulatory networks were constructed. This study provided evidence that alcohol could induce concerted miRNA and mRNA expression changes in reward-related or alcohol-responsive brain regions. We concluded that altered brain miRNA–mRNA regulatory networks might contribute to AUD development.
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影响因子：
14.9
作者：
Kozomara A;Griffiths-Jones S
通讯作者：
Griffiths-Jones S
影响因子：
4.7
作者：
Chen, Suzhen;Charness, Michael E.
通讯作者：
Charness, Michael E.
影响因子：
2.9
作者：
Iwamoto, K;Bundo, M;Kato, T
通讯作者：
Kato, T
影响因子：
23.9
作者：
Maroof, Asif M.;Keros, Sotirios;Tyson, Jennifer A.;Ying, Shui-Wang;Ganat, Yosif M.;Merkle, Florian T.;Liu, Becky;Goulburn, Adam;Stanley, Edouard G.;Elefanty, Andrew G.;Widmer, Hans Ruedi;Eggan, Kevin;Goldstein, Peter A.;Anderson, Stewart A.;Studer, Lorenz
通讯作者：
Studer, Lorenz
DOI：
10.1097/01.alc.0000036926.46632.57
发表时间：
2002-11-01
影响因子：
3.2
作者：
Mandrekar, P;Dolganiuc, A;Szabo, G
通讯作者：
Szabo, G