Expression of glutamatergic genes in healthy humans across 16 brain regions; altered expression in the hippocampus after chronic exposure to alcohol or cocaine.
Expression of glutamatergic genes in healthy humans across 16 brain regions; altered expression in the hippocampus after chronic exposure to alcohol or cocaine.
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DOI：
10.1111/gbb.12179
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Goldman D
中科院分区：
文献类型：
--
作者：
Enoch MA;Rosser AA;Zhou Z;Mash DC;Yuan Q;Goldman D
在确定慢性酒精和可卡因暴露对海马基因表达的影响之前，我们分析了健康成人大脑中与海马神经传递相关的基因（海马神经传递基因）的全球表达模式。来自BrainSpan的RNA-Seq数据来自9名对照成年人的16个大脑区域。我们还从8名酗酒者、8名可卡因成瘾者和8名对照者的死后海马体中生成了RNA-Seq数据。表达分析进行了28个基因编码谷氨酸离子型（AMPA，红藻氨酸，NMDA）和代谢型受体亚基，连同谷氨酸转运蛋白。除了小脑、丘脑背内侧核和纹状体外，每个基因在大脑中的表达都相当一致。GRIN 1编码必需的NMDA亚基，在所有脑区中表达最高。六个因素解释了84%的全球基因表达的方差。GRIN 2B（编码GluN 2B）在酗酒者和可卡因成瘾者中均上调（FDR校正p = 0.008）。与对照组和可卡因成瘾者相比，酗酒者显示出三种基因的上调：GRIA 4（编码GluA 4），GRIK 3（GluR 7）和GRM 4（mGluR 4）。GRM 3（mGluR 3）和GRIN 2D（GluN 2D）的表达在酗酒者中上调，在可卡因成瘾者中下调。谷氨酸能基因在整个大脑中中度至高度表达。六个因素解释了全球基因表达的几乎所有差异。至少在海马体中，长期饮酒在很大程度上上调了海马体能基因。NMDA GluN 2B受体亚基可能与GABAB 1受体亚基一起参与成瘾的共同途径。
We analyzed global patterns of expression in genes related to glutamatergic neurotransmission (glutamatergic genes) in healthy human adult brain before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus. RNA-Seq data from ‘BrainSpan’ was obtained across 16 brain regions from nine control adults. We also generated RNA-Seq data from postmortem hippocampus from eight alcoholics, eight cocaine addicts and eight controls. Expression analyses were undertaken of 28 genes encoding glutamate ionotropic (AMPA, kainate, NMDA) and metabotropic receptor subunits, together with glutamate transporters. The expression of each gene was fairly consistent across the brain with the exception of the cerebellum, the thalamic mediodorsal nucleus and the striatum. GRIN1, encoding the essential NMDA subunit, had the highest expression across all brain regions. Six factors accounted for 84% of the variance in global gene expression. GRIN2B (encoding GluN2B), was up-regulated in both alcoholics and cocaine addicts (FDR corrected p = 0.008). Alcoholics showed up-regulation of three genes relative to controls and cocaine addicts: GRIA4 (encoding GluA4), GRIK3 (GluR7) and GRM4 (mGluR4). Expression of both GRM3 (mGluR3) and GRIN2D (GluN2D) was up-regulated in alcoholics and down-regulated in cocaine addicts relative to controls. Glutamatergic genes are moderately to highly expressed throughout the brain. Six factors explain nearly all the variance in global gene expression. At least in the hippocampus, chronic alcohol use largely up-regulates glutamatergic genes. The NMDA GluN2B receptor subunit might be implicated in a common pathway to addiction, possibly in conjunction with the GABAB1 receptor subunit.
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影响因子：
3.7
作者：
Mash DC;ffrench-Mullen J;Adi N;Qin Y;Buck A;Pablo J
通讯作者：
Pablo J
影响因子：
5.7
作者：
Chalifoux JR;Carter AG
通讯作者：
Carter AG
DOI：
10.1126/science.1204622
发表时间：
2011-07-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Luo AH;Tahsili-Fahadan P;Wise RA;Lupica CR;Aston-Jones G
通讯作者：
Aston-Jones G
DOI：
10.1111/j.1749-6632.2009.05144.x
发表时间：
2010-01-01
期刊：
ADDICTION REVIEWS 2
影响因子：
--
作者：
Schmidt, Heath D.;Pierce, R. Christopher
通讯作者：
Pierce, R. Christopher
影响因子：
16.2
作者：
Chalifoux JR;Carter AG
通讯作者：
Carter AG