Gene expression profiling in the human alcoholic brain.

paper Cited Public

Authors: Warden, Anna S; Mayfield, R Dayne
Year: 2017
Journal: Neuropharmacology
PMID: 28254370
DOI: 10.1016/j.neuropharm.2017.02.017
PMCID: PMC5479716

Figure 1

A hypothetical diagram for the role of transcriptional regulation in AUD. Chronic alcohol consumption can alter regulation of transcription via epigenetic modifications, including miRNAs and lncRNAs. Alterations in these regulatory mechanisms result in aberrant downstream gene expression changes in functional systems known to contribute to alcohol dependence (e.g. neuronal transmission, ion channels, immune signaling, stress response).

LLM interpretation

This is a conceptual diagram illustrating the proposed mechanism by which chronic alcohol consumption leads to Alcohol Use Disorder (AUD). The flowchart shows that chronic alcohol consumption causes alterations in the regulation of transcription via three pathways: epigenetic markers/histone modifications, miRNAs, and long non-coding RNAs. These regulatory changes lead to aberrant gene expression changes across various biological systems (e.g., neurotransmission, stress and immune signaling, metabolism), ultimately resulting in AUD.

Figure 2

Total tissue versus cell-type specific analyses. Left Panel: Example volcano plot from an analysis of a cell-type specific isolation. The wider distribution of the plot signifies a greater number of statistically significant differentially expressed genes associated with chronic alcohol exposure. Right Panel: Example volcano plot from an analysis of a total tissue preparation. Note the smaller distribution and fewer statistically significant differentially expressed genes. Example data source: (https://raw.githubusercontent.com/brennanpincardiff/RforBiochemists/master/data/microArrayData.tsv”).

LLM interpretation

This figure consists of two volcano plots comparing gene expression changes associated with chronic alcohol exposure. The x-axis represents the $\log_2$ fold change and the y-axis represents the $-\log_{10}$ p-value. The left panel (cell-type specific isolation) shows a wider distribution of points with a higher density of statistically significant genes (blue) compared to the right panel (total tissue preparation), which exhibits a smaller distribution and fewer significant genes.

Figure 3

RNA-seq systems approach for understanding alcohol dependence. Sequencing can be used to evaluate changes in regulation of DNA and RNA expression in human alcoholic and control cases. Information from sequencing can then be superimposed with other variables such as protein data, physiological function, or other phenotypic information to identify mechanisms and potential treatment options for AUD. Adapted from (Farris and Mayfield, 2014).

LLM interpretation

This is a conceptual diagram illustrating a systems biology approach to understanding alcohol use disorder (AUD) in the human brain. The figure displays a hierarchical flow of biological information across six levels: DNA regulation/epigenetics, RNA expression, RNA regulation (lncRNAs, miRNAs), protein expression, anatomical-physiological data, and phenotypes. Interconnected nodes and vertical dashed lines indicate the integration of data across these different molecular and physiological layers, with additional external influences noted as other tissues, environment, and the microbiome.

#	Section	Preview
0	1. Introduction	Alcohol use disorder (AUD) involves a progression from impulsive to compulsive drinking behavior…
1	1. Introduction	In individuals escalating to alcohol dependence, there is a complex interplay among predisposition…
2	1. Introduction	Since the introduction of microarray technology, transcriptome profiling of human postmortem brain…
3	1. Introduction	Recent developments in bioinformatics and sequencing techniques have allowed analyses to shift from…
4	1. Introduction	One particular challenge of the post-genomic “big data” era is to determine the degree to which…
5	1. Introduction	inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) as having a modulatory role in…
6	1. Introduction	In the following sections, we describe the factors that influence the reliability and consistency of…
7	2. Human postmortem tissue quality control	Human donor tissue is limited, and there are often difficulties in establishing proper control…
8	2. Human postmortem tissue quality control	Postmortem interval, agonal state, and tissue pH have all been found to weakly correlate with RNA…
9	2. Human postmortem tissue quality control	expression and these variables thus appears to be transcript specific rather than an overall…
10	2. Human postmortem tissue quality control	Besides general quality control measures, additional factors must be considered when designing…
11	2. Human postmortem tissue quality control	use, exclusion of concomitant diseases is not necessarily a requirement for all studies. Concomitant…
12	2. Human postmortem tissue quality control	the duration of ethanol consumption in mouse models of excessive drinking (Osterndorff-Kahanek et…
13	3. Biological co-expression networks: Transcriptional regulation in alcohol use disorder	Although many genes are differentially expressed in the brains of alcoholic subjects, the observed…
14	3. Biological co-expression networks: Transcriptional regulation in alcohol use disorder	WGCNA of human brain tissue has been valuable in the identification of cell-type specific networks…
15	3. Biological co-expression networks: Transcriptional regulation in alcohol use disorder	postmortem prefrontal cortex revealed that gene network structure was significantly correlated with…
16	3. Biological co-expression networks: Transcriptional regulation in alcohol use disorder — 3.1: Epigenetic modifications in the human alcoholic brain	Bleich and Hillemacher (2009) initially demonstrated that alcohol alters DNA methylation and…
17	3. Biological co-expression networks: Transcriptional regulation in alcohol use disorder — 3.1: Epigenetic modifications in the human alcoholic brain	2012). In addition, alcohol-induced up-regulation of genes in GC-rich modules is hypothesized to be…
18	3. Biological co-expression networks: Transcriptional regulation in alcohol use disorder — 3.1: Epigenetic modifications in the human alcoholic brain	System-wide epigenetic modifications have also been observed in the hippocampus of human alcoholics…
19	3. Biological co-expression networks: Transcriptional regulation in alcohol use disorder — 3.1: Epigenetic modifications in the human alcoholic brain	cocaine users (Farris et al., 2015a). In contrast to the modest effects observed previously (Zhou et…

Citation	PMID	DOI	Status
Adachi, Y et al., Gastroenterology, 1995, Antibiotics prevent liver injury in rats following long-term exposure to ethanol	7806045	10.1016/0016-5085(95)90027-6	Cited
Agrawal, A et al., Alcohol Res, 2012, Identifying genetic variation for alcohol dependence	23134043	10.35946/arcr.v34.3.02	Primary
Agudelo, M et al., Alcohol Clin Exp Res, 2011, Effects of alcohol on histone deacetylase 2 (HDAC2) and the neuroprotective role of trichostatin A (TSA)	21447001	10.1111/j.1530-0277.2011.01492.x	Cited
Agudelo, M et al., Alcohol, 2012, Alcohol-induced serotonergic modulation: the role of histone deacetylases	22796363	10.1016/j.alcohol.2012.03.005	Cited
Alaux-Cantin, S et al., Neuropharmacology, 2013, Alcohol intoxications during adolescence increase motivation for alcohol in adult rats and induce neuroadaptations in the nucleus accumbens	23287538	10.1016/j.neuropharm.2012.12.007	Cited
Albertson, DN et al., J Neurochem, 2004, Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin	15009677	10.1046/j.1471-4159.2003.02247.x	Cited
Alexander, RP et al., Nat Rev Genet, 2010, Annotating noncoding regions of the genome	20628352	10.1038/nrg2814	Cited
Alfonso-Loeches, S et al., J Neurosci, 2010, Pivotal role of TLR4 receptors in alcohol-induced neuroinflammation and brain damage	20554880	10.1523/JNEUROSCI.0976-10.2010	Cited
Armario, A, Trends Pharmacol Sci, 2010, Activation of the hypothalamic-pituitary-adrenal axis by addictive drugs: different pathways, common outcome	20537734	10.1016/j.tips.2010.04.005	Cited
Arora, DS et al., Neuropsychopharmacology, 2013, Hyposensitivity to gamma-aminobutyric acid in the ventral tegmental area during alcohol withdrawal: reversal by histone deacetylase inhibitors	23474591	10.1038/npp.2013.65	Cited
Asada, H et al., Biochem Biophys Res Commun, 1996, Mice lacking the 65 kDa isoform of glutamic acid decarboxylase (GAD65) maintain normal levels of GAD67 and GABA in their brains but are susceptible to seizures	8954991	10.1006/bbrc.1996.1898	Cited
Asquith, M et al., Alcohol Clin Exp Res, 2014, Chronic ethanol consumption modulates growth factor release, mucosal cytokine production, and microRNA expression in nonhuman primates	24329418	10.1111/acer.12325	Cited
Barry, G et al., Mol Psychiatry, 2014, The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing	23628989	10.1038/mp.2013.45	Cited
Barton, AJ et al., J Neurochem, 1993, Pre- and postmortem influences on brain RNA	7685811	10.1111/j.1471-4159.1993.tb03532.x	Cited
Belgard, TG et al., Neuron, 2011, A transcriptomic atlas of mouse neocortical layers	21867878	10.1016/j.neuron.2011.06.039	Cited
Bennett, ML et al., Proc Natl Acad Sci U S A, 2016, New tools for studying microglia in the mouse and human CNS	26884166	10.1073/pnas.1525528113	Cited
Bernard, D et al., EMBO J, 2010, A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression	20729808	10.1038/emboj.2010.199	Cited
Bettinger, JC et al., Front Physiol, 2014, The role of the BK channel in ethanol response behaviors: evidence from model organism and human studies	25249984	10.3389/fphys.2014.00346	Cited
Bond, AM et al., Nat Neurosci, 2009, Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry	19620975	10.1038/nn.2371	Cited
Bonsch, D et al., Alcohol Clin Exp Res, 2005, Alpha-synuclein protein levels are increased in alcoholic patients and are linked to craving	15897720	10.1097/01.alc.0000164360.43907.24	Cited
Breving, K et al., Int J Biochem Cell Biol, 2010, The complexities of microRNA regulation: mirandering around the rules	19800023	10.1016/j.biocel.2009.09.016	Cited
Burgoyne, RD et al., Nat Cell Biol, 2011, Chaperoning the SNAREs: a role in preventing neurodegeneration?	21173802	10.1038/ncb0111-8	Cited
Burre, J et al., Science, 2010, Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro	20798282	10.1126/science.1195227	Cited
Carninci, P et al., Curr Opin Genet Dev, 2007, Noncoding RNA transcription beyond annotated genes	17317145	10.1016/j.gde.2007.02.008	Cited
Carninci, P et al., Science, 2005, The transcriptional landscape of the mammalian genome	16141072	10.1126/science.1112014	Cited
Cech, TR et al., Cell, 2014, The noncoding RNA revolution-trashing old rules to forge new ones	24679528	10.1016/j.cell.2014.03.008	Cited
Cesana, M et al., Cell, 2011, A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA	22000014	10.1016/j.cell.2011.09.028	Cited
Chandrasekar, V et al., Mol Cell Neurosci, 2009, microRNAs miR-124, let-7d and miR-181a regulate cocaine-induced plasticity	19703567	10.1016/j.mcn.2009.08.009	Cited
Chen, C et al., Mol Psychiatry, 2013, Two gene co-expression modules differentiate psychotics and controls	23147385	10.1038/mp.2012.146	Cited
Chen, JF et al., Nat Genet, 2006, The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation	16380711	10.1038/ng1725	Cited
Clark, SL et al., Alcohol Clin Exp Res, 2015, Combined Whole Methylome and Genomewide Association Study Implicates CNTN4 in Alcohol Use	26146898	10.1111/acer.12790	Cited
Contet, C, Curr Psychopharmacol, 2012, Gene Expression Under the Influence: Transcriptional Profiling of Ethanol in the Brain	24078902	10.2174/2211556011201040301	Cited
Coveney, PV et al., Philos Trans A Math Phys Eng Sci, 2016, Big data need big theory too	27698035	10.1098/rsta.2016.0153	Cited
Crews, FT et al., Biol Psychiatry, 2013, High mobility group box 1/Toll-like receptor danger signaling increases brain neuroimmune activation in alcohol dependence	23206318	10.1016/j.biopsych.2012.09.030	Cited
Crews, FT et al., Brain Behav Immun, 2011, Induction of innate immune genes in brain create the neurobiology of addiction	21402143	10.1016/j.bbi.2011.03.003	Cited
Crews, FT et al., Psychopharmacology (Berl), 2016, Mechanisms of neuroimmune gene induction in alcoholism	25787746	10.1007/s00213-015-3906-1	Cited
Darmanis, S et al., Proc Natl Acad Sci U S A, 2015, A survey of human brain transcriptome diversity at the single cell level	26060301	10.1073/pnas.1507125112	Cited
Davies, DL et al., Alcohol Clin Exp Res, 2003, Ethanol potentiation of glycine receptors expressed in Xenopus oocytes antagonized by increased atmospheric pressure	12766618	10.1097/01.ALC.0000065722.31109.A1	Cited
Dekker, J, Genome Biol, 2007, GC- and AT-rich chromatin domains differ in conformation and histone modification status and are differentially modulated by Rpd3p	17577398	10.1186/gb-2007-8-6-r116	Cited
Derrien, T et al., Genome Res, 2012, The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression	22955988	10.1101/gr.132159.111	Cited
Doxakis, E, J Biol Chem, 2010, Post-transcriptional regulation of alpha-synuclein expression by mir-7 and mir-153	20106983	10.1074/jbc.M109.086827	Cited
Doyle, JP et al., Cell, 2008, Application of a translational profiling approach for the comparative analysis of CNS cell types	19013282	10.1016/j.cell.2008.10.029	Cited
Ducci, F et al., Psychiatr Clin North Am, 2012, The genetic basis of addictive disorders	22640768	10.1016/j.psc.2012.03.010	Cited
D’Souza, MS, Front Neurosci, 2015, Glutamatergic transmission in drug reward: implications for drug addiction	26594139	10.3389/fnins.2015.00404	Cited
Edenberg, HJ et al., Addict Biol, 2006, The genetics of alcoholism: identifying specific genes through family studies	16961766	10.1111/j.1369-1600.2006.00035.x	Primary
Edenberg, HJ et al., Human Molecular Genetics, 2008, Association of NFKB1, which encodes a subunit of the transcription factor NF-κB, with alcohol dependence	18079108	10.1093/hmg/ddm368	Primary
Ellis, FW, J Pharmacol Exp Ther, 1966, Effect of ethanol on plasma corticosterone levels	4288396	—	Cited
Enoch, MA et al., Neuropsychopharmacology, 2009, GABRG1 and GABRA2 as independent predictors for alcoholism in two populations	18818659	10.1038/npp.2008.171	Cited
Enoch, MA et al., PLoS One, 2012, GABAergic gene expression in postmortem hippocampus from alcoholics and cocaine addicts; corresponding findings in alcohol-naive P and NP rats	22253714	10.1371/journal.pone.0029369	Cited
Enoch, MA et al., PLoS One, 2013, A factor analysis of global GABAergic gene expression in human brain identifies specificity in response to chronic alcohol and cocaine exposure	23717525	10.1371/journal.pone.0064014	Cited
Falkenberg, KJ et al., Nat Rev Drug Discov, 2014, Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders	25131830	10.1038/nrd4360	Cited
Farris, SP et al., Front Neurosci, Epigenetic modulation of brain gene networks for cocaine and alcohol abuse	26041984	10.3389/fnins.2015.00176	Cited
Farris, SP et al., Int Rev Neurobiol, 2014, RNA-Seq reveals novel transcriptional reorganization in human alcoholic brain	25172479	10.1016/B978-0-12-801105-8.00011-4	Cited
Farris, SP et al., Mol Psychiatry, Transcriptome organization for chronic alcohol abuse in human brain	25450227	10.1038/mp.2014.159	Cited
Filipowicz, W et al., Nat Rev Genet, 2008, Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?	18197166	10.1038/nrg2290	Cited
Fiorenza, A et al., Neurobiol Learn Mem, 2016, Role of Dicer and the miRNA system in neuronal plasticity and brain function	27163737	10.1016/j.nlm.2016.05.001	Cited
Frank, MG et al., Brain Behav Immun, 2010, Prior exposure to glucocorticoids sensitizes the neuroinflammatory and peripheral inflammatory responses to E. coli lipopolysaccharide	19647070	10.1016/j.bbi.2009.07.008	Cited
Friedman, RC et al., Genome Res, 2009, Most mammalian mRNAs are conserved targets of microRNAs	18955434	10.1101/gr.082701.108	Cited
Garate, I et al., Biol Psychiatry, 2013, Stress-induced neuroinflammation: role of the Toll-like receptor-4 pathway	22906518	10.1016/j.biopsych.2012.07.005	Cited
Gelernter, J et al., Mol Psychiatry, 2014, Genome-wide association study of alcohol dependence:significant findings in African- and European-Americans including novel risk loci	24166409	10.1038/mp.2013.145	Primary
Gorini, G et al., PLoS ONE, Integration of miRNA and Protein Profiling Reveals Coordinated Neuroadaptations in the Alcohol-Dependent Mouse Brain	24358208	10.1371/journal.pone.0082565	Cited
Gorini, G et al., PLoS ONE, Neurobiological Signatures of Alcohol Dependence Revealed by Protein Profiling	24358215	10.1371/journal.pone.0082656	Cited
Grieco, TM et al., Neuron, 2005, Open-channel block by the cytoplasmic tail of sodium channel beta4 as a mechanism for resurgent sodium current	15664175	10.1016/j.neuron.2004.12.035	Cited
Guttman, M et al., Nature, 2011, lincRNAs act in the circuitry controlling pluripotency and differentiation	21874018	10.1038/nature10398	Cited
Harish, G et al., Neuropathol Appl Neurobiol, 2013, Mitochondrial function in human brains is affected by pre- and post mortem factors	22639898	10.1111/j.1365-2990.2012.01285.x	Cited
Harrison, PJ et al., Neurosci Lett, 1995, The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies: selective mRNA vulnerability and comparison with their encoded proteins	9064599	10.1016/0304-3940(95)12102-a	Cited
Hervouet, E et al., PLoS One, 2010, Disruption of Dnmt1/PCNA/UHRF1 interactions promotes tumorigenesis from human and mice glial cells	20613874	10.1371/journal.pone.0011333	Cited
Jeanblanc, J et al., Int J Neuropsychopharmacol, 2015, The Class I-Specific HDAC Inhibitor MS-275 Decreases Motivation to Consume Alcohol and Relapse in Heavy Drinking Rats	25762717	10.1093/ijnp/pyv029	Cited
Jia, H et al., RNA, 2010, Genome-wide computational identification and manual annotation of human long noncoding RNA genes	20587619	10.1261/rna.1951310	Cited
Johnston, NL et al., J Neurosci Methods, 1997, Multivariate analysis of RNA levels from postmortem human brains as measured by three different methods of RT-PCR. Stanley Neuropathology Consortium	9402561	10.1016/s0165-0270(97)00115-5	Cited
Jones, JD et al., Alcohol Clin Exp Res, 2015, The pharmacogenetics of alcohol use disorder	25703505	10.1111/acer.12643	Cited
Jurd, R et al., J Biol Chem, 2008, Mind bomb-2 is an E3 ligase that ubiquitinates the N-methyl-D-aspartate receptor NR2B subunit in a phosphorylation-dependent manner	17962190	10.1074/jbc.M705580200	Cited
Kalivas, PW et al., Neuropsychopharmacology, 2008, Drug addiction as a pathology of staged neuroplasticity	17805308	10.1038/sj.npp.1301564	Cited
Karahanian, E et al., Alcohol Clin Exp Res, 2011, Ethanol as a prodrug: brain metabolism of ethanol mediates its reinforcing effects	21332529	10.1111/j.1530-0277.2011.01439.x	Cited
Khalil, AM et al., Proc Natl Acad Sci U S A, 2009, Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression	19571010	10.1073/pnas.0904715106	Cited
Kim, JI et al., Science, 2015, Aldehyde dehydrogenase 1a1 mediates a GABA synthesis pathway in midbrain dopaminergic neurons	26430123	10.1126/science.aac4690	Cited
Kocerha, J et al., Mol Psychiatry, 2015, Noncoding RNAs and neurobehavioral mechanisms in psychiatric disease	25824307	10.1038/mp.2015.30	Cited
Koob, GF et al., Lancet Psychiatry, 2016, Neurobiology of addiction: a neurocircuitry analysis	27475769	10.1016/S2215-0366(16)00104-8	Cited
Koob, GF et al., Nat Neurosci, 2005, Plasticity of reward neurocircuitry and the ‘dark side’ of drug addiction	16251985	10.1038/nn1105-1442	Cited
Koob, GF et al., Neuropsychopharmacology, 2010, Neurocircuitry of addiction	19710631	10.1038/npp.2009.110	Cited
Koomoa, DL et al., Neurosci Lett, 2008, Expression profile of PRAF2 in the human brain and enrichment in synaptic vesicles	18395978	10.1016/j.neulet.2008.03.030	Cited
Krishnaswami, SR et al., Nat Protoc, 2016, Using single nuclei for RNA-seq to capture the transcriptome of postmortem neurons	26890679	10.1038/nprot.2016.015	Cited
Kryger, R et al., Alcohol, 2012, MALAT-1, a non protein-coding RNA is upregulated in the cerebellum, hippocampus and brain stem of human alcoholics	22560368	10.1016/j.alcohol.2012.04.002	Cited
Lee, JH et al., Science, 2014, Highly multiplexed subcellular RNA sequencing in situ	24578530	10.1126/science.1250212	Cited
Lee, JT, Science, 2012, Epigenetic regulation by long noncoding RNAs	23239728	10.1126/science.1231776	Cited
Legastelois, R et al., Alcohol Clin Exp Res, 2013, Blockade of ethanol-induced behavioral sensitization by sodium butyrate: descriptive analysis of gene regulations in the striatum	23488934	10.1111/acer.12088	Cited
Leung, JG et al., Ann Pharmacother, 2015, The role of gabapentin in the management of alcohol withdrawal and dependence	25969570	10.1177/1060028015585849	Cited
Lewohl, JM et al., Alcohol Clin Exp Res, 2000, Gene expression in human alcoholism: microarray analysis of frontal cortex	11141048	—	Cited
Lewohl, JM et al., Alcohol Clin Exp Res, 2011, Up-regulation of microRNAs in brain of human alcoholics	21651580	10.1111/j.1530-0277.2011.01544.x	Cited
Li, D et al., Neuropsychopharmacology, 2014, Association of gamma-aminobutyric acid A receptor alpha2 gene (GABRA2) with alcohol use disorder	24136292	10.1038/npp.2013.291	Cited
Li, JZ et al., Hum Mol Genet, 2004, Systematic changes in gene expression in postmortem human brains associated with tissue pH and terminal medical conditions	14734628	10.1093/hmg/ddh065	Cited
Lippai, D et al., J Leukoc Biol, 2013, Alcohol-induced IL-1β in the brain is mediated by NLRP3/ASC inflammasome activation that amplifies neuroinflammation	23625200	10.1189/jlb.1212659	Cited
Lipska, BK et al., Biol Psychiatry, 2006, Critical factors in gene expression in postmortem human brain: Focus on studies in schizophrenia	16997002	10.1016/j.biopsych.2006.06.019	Cited
Liu, J et al., Alcohol Clin Exp Res, 2007, Altered gene expression profiles in the frontal cortex of cirrhotic alcoholics	17625000	10.1111/j.1530-0277.2007.00444.x	Cited
Liu, J et al., J Neurochem, 2004, Gene expression profiling of individual cases reveals consistent transcriptional changes in alcoholic human brain	15312160	10.1111/j.1471-4159.2004.02570.x	Cited
Liu, J et al., Neuropsychopharmacology, 2006, Patterns of gene expression in the frontal cortex discriminate alcoholic from nonalcoholic individuals	16292326	10.1038/sj.npp.1300947	Cited
Longo, LP et al., J Addict Dis, 2002, Divalproex sodium (Depakote) for alcohol withdrawal and relapse prevention	11916372	10.1300/J069v21n02_05	Cited
Lopez-Moreno, JA et al., Alcohol Clin Exp Res, 2015, Histone Deacetylase Gene Expression Following Binge Alcohol Consumption in Rats and Humans	26365275	10.1111/acer.12850	Cited
Lovatt, D et al., Nat Methods, 2014, Transcriptome in vivo analysis (TIVA) of spatially defined single cells in live tissue	24412976	10.1038/nmeth.2804	Cited
Malan-Muller, S et al., Mol Neurobiol, 2013, Big effects of small RNAs: a review of microRNAs in anxiety	23150170	10.1007/s12035-012-8374-6	Cited
Mamdani, M et al., PLoS One, 2015, Integrating mRNA and miRNA Weighted Gene Co-Expression Networks with eQTLs in the Nucleus Accumbens of Subjects with Alcohol Dependence	26381263	10.1371/journal.pone.0137671	Primary
Manzardo, AM et al., Alcohol Clin Exp Res, 2014, Exon microarray analysis of human dorsolateral prefrontal cortex in alcoholism	24890784	10.1111/acer.12429	Cited
Manzo-Avalos, S et al., Int J Environ Res Public Health, 2010, Cellular and mitochondrial effects of alcohol consumption	21318009	10.3390/ijerph7124281	Cited
Massone, S et al., Neurobiol Dis, 2011, 17A, a novel non-coding RNA, regulates GABA B alternative splicing and signaling in response to inflammatory stimuli and in Alzheimer disease	20888417	10.1016/j.nbd.2010.09.019	Cited
Mayfield, J et al., Curr Opin Neurobiol, 2013, Neuroimmune signaling: a key component of alcohol abuse	23434064	10.1016/j.conb.2013.01.024	Cited
Mayfield, J et al., Int Rev Neurobiol, 2016, Genes and Alcohol Consumption: Studies with Mutant Mice	27055617	10.1016/bs.irn.2016.02.014	Cited
Mayfield, RD et al., J Neurochem, 2002, Patterns of gene expression are altered in the frontal and motor cortices of human alcoholics	12065639	10.1046/j.1471-4159.2002.00860.x	Cited
McClintick, JN et al., Alcohol, 2013, Stress-response pathways are altered in the hippocampus of chronic alcoholics	23981442	10.1016/j.alcohol.2013.07.002	Primary
Mercer, TR et al., Nat Rev Genet, 2009, Long non-coding RNAs: insights into functions	19188922	10.1038/nrg2521	Cited
Mercer, TR et al., Proc Natl Acad Sci U S A, 2008, Specific expression of long noncoding RNAs in the mouse brain	18184812	10.1073/pnas.0706729105	Cited
Michelhaugh, SK et al., J Neurochem, 2011, Mining Affymetrix microarray data for long non-coding RNAs: altered expression in the nucleus accumbens of heroin abusers	21128942	10.1111/j.1471-4159.2010.07126.x	Cited
Minones-Moyano, E et al., Hum Mol Genet, 2011, MicroRNA profiling of Parkinson’s disease brains identifies early downregulation of miR-34b/c which modulate mitochondrial function	21558425	10.1093/hmg/ddr210	Cited
Miranda, RC et al., Alcohol Clin Exp Res, 2010, MicroRNAs: master regulators of ethanol abuse and toxicity?	20102566	10.1111/j.1530-0277.2009.01126.x	Cited
Moonat, S et al., Alcohol Res, 2012, Stress, epigenetics, and alcoholism	23584115	10.35946/arcr.v34.4.13	Cited
Mulligan, MK et al., Proc Natl Acad Sci U S A, 2006, Toward understanding the genetics of alcohol drinking through transcriptome meta-analysis	16618939	10.1073/pnas.0510188103	Cited
Myrick, H et al., Am J Drug Alcohol Abuse, 2000, Divalproex in the treatment of alcohol withdrawal	10718170	10.1081/ada-100100597	Cited
Nature, 2012, An integrated encyclopedia of DNA elements in the human genome	22955616	10.1038/nature11247	Cited
Nica, AC et al., Philos Trans R Soc Lond B Biol Sci, 2013, Expression quantitative trait loci: present and future	23650636	10.1098/rstb.2012.0362	Cited
Nunez, YO et al., BMC Genomics, 2013, Positively correlated miRNA-mRNA regulatory networks in mouse frontal cortex during early stages of alcohol dependence	24148570	10.1186/1471-2164-14-725	Cited
Nunez, YO et al., Front Genet, 2012, Understanding Alcoholism Through microRNA Signatures in Brains of Human Alcoholics	22514554	10.3389/fgene.2012.00043	Cited
Oldham, MC et al., Nat Neurosci, 2008, Functional organization of the transcriptome in human brain	18849986	10.1038/nn.2207	Cited
Osterndorff-Kahanek, E et al., PLoS One, 2013, Gene expression in brain and liver produced by three different regimens of alcohol consumption in mice: comparison with immune activation	23555817	10.1371/journal.pone.0059870	Cited
Osterndorff-Kahanek, EA et al., PLoS One, 2015, Chronic ethanol exposure produces time- and brain region-dependent changes in gene coexpression networks	25803291	10.1371/journal.pone.0121522	Cited
Oyama, F et al., J Neurochem, 2006, Sodium channel beta4 subunit: down-regulation and possible involvement in neuritic degeneration in Huntington’s disease transgenic mice	16805843	10.1111/j.1471-4159.2006.03893.x	Cited
Pandey, SC et al., J Neurosci, 2008, Brain chromatin remodeling: a novel mechanism of alcoholism	18385331	10.1523/JNEUROSCI.5731-07.2008	Cited
Pascual, M et al., Neuropharmacology, 2012, Changes in histone acetylation in the prefrontal cortex of ethanol-exposed adolescent rats are associated with ethanol-induced place conditioning	22349397	10.1016/j.neuropharm.2012.01.011	Cited
Pastor, IJ et al., Alcohol Alcohol, 2005, Interleukin-1 gene cluster polymorphisms and alcoholism in Spanish men	15797878	10.1093/alcalc/agh153	Cited
Pastor, IJ et al., Alcoholism: Clinical and Experimental Research, 2000, Polymorphism in the Interleukin-1 Receptor Antagonist Gene Is Associated With Alcoholism in Spanish Men	11045853	—	Cited
Pfefferbaum, A et al., Alcohol Clin Exp Res, 1997, Frontal lobe volume loss observed with magnetic resonance imaging in older chronic alcoholics	9161613	10.1111/j.1530-0277.1997.tb03798.x	Cited
Pietrzykowski, AZ et al., Neuron, 2008, Posttranscriptional regulation of BK channel splice variant stability by miR-9 underlies neuroadaptation to alcohol	18667155	10.1016/j.neuron.2008.05.032	Cited
Pillai, RS et al., Science, 2005, Inhibition of translational initiation by Let-7 MicroRNA in human cells	16081698	10.1126/science.1115079	Cited
Ponomarev, I et al., J Neurosci, 2012, Gene coexpression networks in human brain identify epigenetic modifications in alcohol dependence	22302827	10.1523/JNEUROSCI.3136-11.2012	Cited
Ponomarev, I et al., Neuropsychopharmacology, 2010, Amygdala transcriptome and cellular mechanisms underlying stress-enhanced fear learning in a rat model of posttraumatic stress disorder	20147889	10.1038/npp.2010.10	Cited
Qin, L et al., Glia, 2007, Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration	17203472	10.1002/glia.20467	Cited
Quertemont, E et al., Prog Neurobiol, 2005, The role of acetaldehyde in the neurobehavioral effects of ethanol: a comprehensive review of animal studies	15882776	10.1016/j.pneurobio.2005.03.003	Cited
Ravasi, T et al., Genome Res, 2006, Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome	16344565	10.1101/gr.4200206	Cited
Robinson, G et al., Int Rev Neurobiol, 2014, Neuroimmune pathways in alcohol consumption: evidence from behavioral and genetic studies in rodents and humans	25175860	10.1016/B978-0-12-801284-0.00002-6	Cited
Saba, R et al., Mol Cell Biol, 2012, Dopamine-regulated microRNA MiR-181a controls GluA2 surface expression in hippocampal neurons	22144581	10.1128/MCB.05896-11	Cited
Saito, Y et al., Front Genet, 2012, MicroRNAs in cancers and neurodegenerative disorders	23056009	10.3389/fgene.2012.00194	Cited
Saiz, PA et al., Alcohol Clin Exp Res, 2009, Polymorphisms of the IL-1 gene complex are associated with alcohol dependence in Spanish Caucasians: data from an association study	19764937	10.1111/j.1530-0277.2009.01058.x	Cited
Sakharkar, AJ et al., Int J Neuropsychopharmacol, 2014, Effects of acute ethanol exposure on anxiety measures and epigenetic modifiers in the extended amygdala of adolescent rats	24968059	10.1017/S1461145714001047	Cited
Sartor, GC et al., Front Genet, 2012, The Emerging Role of Non-Coding RNAs in Drug Addiction	22737160	10.3389/fgene.2012.00106	Cited
Sato, F et al., FEBS J, 2011, MicroRNAs and epigenetics	21395977	10.1111/j.1742-4658.2011.08089.x	Cited
Schaller, KL et al., J Comp Neurol, 2000, Developmental and regional expression of sodium channel isoform NaCh6 in the rat central nervous system	10745221	—	Cited
Shin, C et al., Expert Rev Neurother, 2016, Precision medicine for psychopharmacology: a general introduction	27104961	10.1080/14737175.2016.1182022	Cited
Sliwczynski, A et al., Pol Arch Med Wewn, 2016, Precision medicine for managing chronic diseases	27535198	10.20452/pamw.3503	Cited
Smalheiser, NR et al., PLoS One, 2014, Expression of microRNAs and other small RNAs in prefrontal cortex in schizophrenia, bipolar disorder and depressed subjects	24475125	10.1371/journal.pone.0086469	Cited
Smith, SS et al., Nature, 1998, GABA(A) receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid	9582073	10.1038/31948	Cited
Sokolov, BP, Int J Neuropsychopharmacol, 2007, Oligodendroglial abnormalities in schizophrenia, mood disorders and substance abuse. Comorbidity, shared traits, or molecular phenocopies?	17291372	10.1017/S1461145706007322	Cited
Spence, JP et al., Curr Drug Abuse Rev, 2009, From QTL to candidate gene: a genetic approach to alcoholism research	19630743	10.2174/1874473710902020127	Cited
Srinivasan, K et al., Nat Commun, 2016, Untangling the brain’s neuroinflammatory and neurodegenerative transcriptional responses	27097852	10.1038/ncomms11295	Cited
Stan, AD et al., Brain Res, 2006, Human postmortem tissue: what quality markers matter?	17045977	10.1016/j.brainres.2006.09.025	Cited
Starkman, BG et al., Alcohol Res, 2012, Epigenetics-beyond the genome in alcoholism	23134045	10.35946/arcr.v34.3.04	Cited
Stephens, MA et al., Alcohol Res, 2012, Stress and the HPA axis: role of glucocorticoids in alcohol dependence	23584113	10.35946/arcr.v34.4.11	Cited
Su, Y et al., FEBS Lett, 2014, MicroRNA-152 targets ADAM17 to suppress NSCLC progression	24780186	10.1016/j.febslet.2014.04.022	Cited
Sugino, K et al., Nat Neurosci, 2006, Molecular taxonomy of major neuronal classes in the adult mouse forebrain	16369481	10.1038/nn1618	Cited
Sureshchandra, S et al., PLoS One, 2016, Transcriptome Profiling Reveals Disruption of Innate Immunity in Chronic Heavy Ethanol Consuming Female Rhesus Macaques	27427759	10.1371/journal.pone.0159295	Cited
Sutherland, GT et al., Alcohol Clin Exp Res, 2014, Using autopsy brain tissue to study alcohol-related brain damage in the genomic age	24033426	10.1111/acer.12243	Cited
Sutherland, GT et al., Alcohol, 2016, The NSW brain tissue resource centre: Banking for alcohol and major neuropsychiatric disorders research	27139235	10.1016/j.alcohol.2016.02.005	Cited
Taganov, KD et al., Proc Natl Acad Sci U S A, 2006, NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses	16885212	10.1073/pnas.0605298103	Cited
Taraskina, AE et al., Bull Exp Biol Med, 2008, High level of alpha-synuclein mRNA in peripheral lymphocytes of patients with alcohol dependence syndrome	19526103	10.1007/s10517-009-0345-1	Cited
Tomita, H et al., Biol Psychiatry, 2004, Effect of agonal and postmortem factors on gene expression profile: quality control in microarray analyses of postmortem human brain	14960286	10.1016/j.biopsych.2003.10.013	Cited
Torkamani, A et al., Genome Res, 2010, Coexpression network analysis of neural tissue reveals perturbations in developmental processes in schizophrenia	20197298	10.1101/gr.101956.109	Cited
Tripathi, V et al., Mol Cell, 2010, The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation	20797886	10.1016/j.molcel.2010.08.011	Cited
Trudell, JR et al., Trends Pharmacol Sci, 2014, Alcohol dependence: molecular and behavioral evidence	24865944	10.1016/j.tips.2014.04.009	Cited
Truitt, JM et al., eneuro, 2016, Inhibition of IKKβ Reduces Ethanol Consumption in C57BL/6J Mice	27822501	10.1523/ENEURO.0256-16.2016	Cited
Tsuruta, T et al., Cancer Res, 2011, miR-152 is a tumor suppressor microRNA that is silenced by DNA hypermethylation in endometrial cancer	21868754	10.1158/0008-5472.CAN-11-0364	Cited
Vallés, SL et al., Brain Pathol, 2004, Chronic ethanol treatment enhances inflammatory mediators and cell death in the brain and in astrocytes	15605983	10.1111/j.1750-3639.2004.tb00079.x	Cited
van Stegeren, AH, Can J Psychiatry, 2009, Imaging stress effects on memory: a review of neuroimaging studies	19175976	10.1177/070674370905400105	Cited
Varambally, S et al., Science, 2008, Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer	19008416	10.1126/science.1165395	Cited
Vasudevan, S et al., Science, 2007, Switching from repression to activation: microRNAs can up-regulate translation	18048652	10.1126/science.1149460	Cited
Volkow, ND et al., N Engl J Med, 2016, Neurobiologic Advances from the Brain Disease Model of Addiction	26816013	10.1056/NEJMra1511480	Cited
Wang, F et al., Sci Rep, 2016, DNA co-methylation modules in postmortem prefrontal cortex tissues of European Australians with alcohol use disorders	26763658	10.1038/srep19430	Cited
Wang, J et al., J Neurosci, 2010, Long-lasting adaptations of the NR2B-containing NMDA receptors in the dorsomedial striatum play a crucial role in alcohol consumption and relapse	20668202	10.1523/JNEUROSCI.2268-10.2010	Cited
Wang, KC et al., Mol Cell, 2011, Molecular mechanisms of long noncoding RNAs	21925379	10.1016/j.molcel.2011.08.018	Cited
Wang, KC et al., Nature, 2011, A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression	21423168	10.1038/nature09819	Cited
Wapinski, O et al., Trends Cell Biol, 2011, Long noncoding RNAs and human disease	21550244	10.1016/j.tcb.2011.04.001	Cited
Warden, A et al., Pharmacogenomics, 2016, The neuroimmune transcriptome and alcohol dependence: potential for targeted therapies	27918243	10.2217/pgs-2016-0062	Cited
Warnault, V et al., Transl Psychiatry, 2013, Chromatin remodeling–a novel strategy to control excessive alcohol drinking	23423140	10.1038/tp.2013.4	Cited
Wellner, U et al., Nat Cell Biol, 2009, The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs	19935649	10.1038/ncb1998	Cited
White, NM, Addiction, 1996, Addictive drugs as reinforcers: multiple partial actions on memory systems	8688822	—	Cited
Xu, X et al., Syst Biomed (Austin), 2013, Cell Type Specific Analysis of Human Brain Transcriptome Data to Predict Alterations in Cellular Composition	25340014	10.4161/sysb.25630	Cited
Yi, Z et al., J Neurosci, 2007, The role of the PDZ protein GIPC in regulating NMDA receptor trafficking	17959809	10.1523/JNEUROSCI.3252-07.2007	Cited
Yu, FH et al., J Neurosci, 2003, Sodium channel beta4, a new disulfide-linked auxiliary subunit with similarity to beta2	12930796	10.1523/JNEUROSCI.23-20-07577.2003	Cited
Zakhari, S, Alcohol Res, 2013, Alcohol metabolism and epigenetics changes	24313160	10.35946/arcr.v35.1.02	Cited
Zhang, H et al., Hum Genet, Differentially co-expressed genes in postmortem prefrontal cortex of individuals with alcohol use disorders: influence on alcohol metabolism-related pathways	25073604	10.1007/s00439-014-1473-x	Cited
Zhang, L et al., Proc Natl Acad Sci U S A, 2004, GC/AT-content spikes as genomic punctuation marks	15548610	10.1073/pnas.0407821101	Cited
Zhang, Y et al., J Neurosci, An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex	25186741	10.1523/JNEUROSCI.1860-14.2014	Cited
Zhang, Y et al., Neuron, 2016, Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse	26687838	10.1016/j.neuron.2015.11.013	Cited
Zhou, Z et al., Proc Natl Acad Sci U S A, 2011, Substance-specific and shared transcription and epigenetic changes in the human hippocampus chronically exposed to cocaine and alcohol	21464311	10.1073/pnas.1018514108	Cited
Ökvist, A et al., PLoS ONE, 2007, Neuroadaptations in Human Chronic Alcoholics: Dysregulation of the NF-κB System	17895971	10.1371/journal.pone.0000930	Cited

In this knowledge base

Title	Year	PMID
Allele-specific expression and high-throughput reporter assay reveal functional genetic variants associated with alcohol use disorders.	2021	31477794

External

Title	Authors	Journal	Year	Link
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Allele-specific expression and high-throughput reporter assay reveal functional genetic variants associated with alcohol use disorders.	Rao X et al.	—	2021	→
Epigenetic landscape of stress surfeit disorders: Key role for DNA methylation dynamics.	Gatta E et al.	—	2021	→
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Regional radiomics similarity networks (R2SNs) in the human brain: Reproducibility, small-world properties and a biological basis.	Zhao K et al.	—	2021	→
Assessing the Role of Long Noncoding RNA in Nucleus Accumbens in Subjects With Alcohol Dependence.	Drake J et al.	—	2020	→
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Flying Together: <i>Drosophila</i> as a Tool to Understand the Genetics of Human Alcoholism.	Lathen DR et al.	—	2020	→
Microglia Control Escalation of Drinking in Alcohol-Dependent Mice: Genomic and Synaptic Drivers.	Warden AS et al.	—	2020	→
Molecular mechanisms of psychiatric diseases.	Blokhin IO et al.	—	2020	→
Network preservation reveals shared and unique biological processes associated with chronic alcohol abuse in NAc and PFC.	Vornholt E et al.	—	2020	→
Phenotypic and gene expression features associated with variation in chronic ethanol consumption in heterogeneous stock collaborative cross mice.	Hitzemann R et al.	—	2020	→
RNA-Seq Analysis of Genetic and Transcriptome Network Effects of Dual-Trait Selection for Ethanol Preference and Withdrawal Using SOT and NOT Genetic Models.	Kozell LB et al.	—	2020	→
The role of the mTOR pathway in models of drug-induced reward and the behavioural constituents of addiction.	Ucha M et al.	—	2020	→
A Pathway-Based Genomic Approach to Identify Medications: Application to Alcohol Use Disorder.	Ferguson LB et al.	—	2019	→
Brain Imaging-Guided Analysis Reveals DNA Methylation Profiles Correlated with Insular Surface Area and Alcohol Use Disorder.	Zhao Y et al.	—	2019	→
Proteomics Reveals Profound Metabolic Changes in the Alcohol Use Disorder Brain.	Enculescu C et al.	—	2019	→
Regional Analysis of the Brain Transcriptome in Mice Bred for High and Low Methamphetamine Consumption.	Hitzemann R et al.	—	2019	→
Silencing synaptic MicroRNA-411 reduces voluntary alcohol consumption in mice.	Most D et al.	—	2019	→
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Testosterone modulation of ethanol effects on the µ-opioid receptor kinetics in castrated rats.	Khalil R et al.	—	2019	→
The importance of long non-coding RNAs in neuropsychiatric disorders.	Hosseini E et al.	—	2019	→
A molecular mechanism for choosing alcohol over an alternative reward.	Augier E et al.	—	2018	→
GABA<sub>A</sub> receptor polymorphisms in alcohol use disorder in the GWAS era.	Koulentaki M et al.	—	2018	→
Long-term ethanol exposure: Temporal pattern of microRNA expression and associated mRNA gene networks in mouse brain.	Osterndorff-Kahanek EA et al.	—	2018	→
Persistent Neuroadaptations in the Expression of Genes Involved in Cholesterol Homeostasis Induced by Chronic, Voluntary Alcohol Intake in Rats.	Alsebaaly J et al.	—	2018	→
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Chronic intermittent ethanol exposure selectively alters the expression of Gα subunit isoforms and RGS subtypes in rat prefrontal cortex.	Luessen DJ et al.	—	2017	→
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The future is now: A 2020 view of alcoholism research.	Harris RA et al.	—	2017	→
The role of neuroimmune signaling in alcoholism.	Crews FT et al.	—	2017	→