{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T07:09:42Z","timestamp":1773472182437,"version":"3.50.1"},"reference-count":63,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,1,25]],"date-time":"2020-01-25T00:00:00Z","timestamp":1579910400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA013484"],"award-info":[{"award-number":["AA013484"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["P600AA010760"],"award-info":[{"award-number":["P600AA010760"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R24AA019431"],"award-info":[{"award-number":["R24AA019431"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Genome\u2010wide profiling to examine brain transcriptional features associated with excessive ethanol (EtOH) consumption has been applied to a variety of species including rodents, nonhuman primates (NHPs), and humans. However, these data were obtained from cross\u2010sectional samples which are particularly vulnerable to individual variation when obtained from small outbred populations typical of human and NHP studies. In the current study, a novel within\u2010subject design was used to examine the effects of voluntary EtOH consumption on prefrontal cortex (PFC) gene expression in a NHP model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two cohorts of cynomolgus macaques (<jats:italic>n<\/jats:italic>\u00a0=\u00a023) underwent a schedule\u2010induced polydipsia procedure to establish EtOH self\u2010administration followed by 6\u00a0months of daily open access to EtOH (4% w\/v) and water. Individual daily EtOH intakes ranged from an average of 0.7 to 3.7\u00a0g\/kg\/d. Dorsal lateral PFC area 46 (A46) brain biopsies were collected in EtOH\u2010na\u00efve and control monkeys; contralateral A46 biopsies were collected from the same monkeys following the 6\u00a0months of fluid consumption. Gene expression changes were assessed using RNA\u2010Seq paired analysis, which allowed for correction of individual baseline differences in gene expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 675 genes were significantly down\u2010regulated following EtOH consumption; these were functionally enriched for immune response, cell adhesion, plasma membrane, and extracellular matrix. A total of 567 genes that were up\u2010regulated following EtOH consumption were enriched in microRNA target sites and included target sites associated with Toll\u2010like receptor pathways. The differentially expressed genes were also significantly enriched in transcription factor binding sites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The data presented here are the first to use a longitudinal biopsy strategy to examine how chronic EtOH consumption affects gene expression in the primate PFC. Prominent effects were seen in both cell adhesion and neuroimmune pathways; the latter contained both pro\u2010 and antiinflammatory genes. The data also indicate that changes in miRNAs and transcription factors may be important epigenetic regulators of EtOH consumption.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14259","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T10:38:17Z","timestamp":1576492697000},"page":"470-478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Chronic Voluntary Ethanol Drinking in Cynomolgus Macaques Elicits Gene Expression Changes in Prefrontal Cortical Area 46"],"prefix":"10.1111","volume":"44","author":[{"given":"Nicole A. R.","family":"Walter","sequence":"first","affiliation":[{"name":"Division of Neuroscience Oregon National Primate Research Center Oregon Health &amp; Science University Beaverton Oregon"},{"name":"Department of Behavioral Neuroscience Oregon Health &amp; Science University Portland Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina L.","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Bioinformatics and Computational Biology Department of Medical Informatics and Clinical Epidemiology Oregon Health &amp; Science University Portland Oregon"},{"name":"Knight Cancer Institute Oregon Health &amp; Science University Portland Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert P.","family":"Searles","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute Oregon Health &amp; Science University Portland Oregon"},{"name":"Integrated Genomics Laboratory Oregon Health &amp; Science University Portland Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shannon K.","family":"McWeeney","sequence":"additional","affiliation":[{"name":"Division of Bioinformatics and Computational Biology Department of Medical Informatics and Clinical Epidemiology Oregon Health &amp; Science University Portland Oregon"},{"name":"Knight Cancer Institute Oregon Health &amp; Science University Portland Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0380-7219","authenticated-orcid":false,"given":"Kathleen A.","family":"Grant","sequence":"additional","affiliation":[{"name":"Division of Neuroscience Oregon National Primate Research Center Oregon Health &amp; Science University Beaverton Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Hitzemann","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neuroscience Oregon Health &amp; Science University Portland Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,1,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw345"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2011.09.024"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12547"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1388-y"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-128"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10519-013-9604-z"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1067"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2018_92"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2010.01385.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/gbb.12367"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/2211556011201040301"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-801284-0.00001-4"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2014.120"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12467"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.616888"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2016.01.024"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-48"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029369"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2018.12.007"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-801105-8.00011-4"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2017.11.036"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhs096"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082565"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2008.00765.x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1999.tb04162.x"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2010.01353.x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.06.001"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2017.02.176"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-13-123"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12501"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13777"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-017-4596-7"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2011.01544.x"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2000.tb01993.x"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070945"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63486-3.00012-8"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0137671"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2013.05.052"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkj143"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13208"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agh086"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510188103"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-725"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0190841"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406454102"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12913"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01038"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21141"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh012"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21552"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy081"},{"key":"e_1_2_9_57_1","unstructured":"2015 Substance Abuse and Mental Health Administration (SAaMHS) National Survey on Drug Use and Health"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12229"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0110484"},{"key":"e_1_2_9_60_1","first-page":"155","article-title":"Differential expression of miR\u2010130a in postmortem prefrontal cortex of subjects with alcohol use disorders","volume":"4","author":"Wang F","year":"2013","journal-title":"J Addict Res Ther"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2018.12.004"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.02.017"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)04036-2"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.148916.112"}],"container-title":["Alcoholism: Clinical and Experimental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Facer.14259","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.14259","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acer.14259","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.14259","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T08:44:17Z","timestamp":1694162657000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acer.14259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,25]]},"references-count":63,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["10.1111\/acer.14259"],"URL":"https:\/\/doi.org\/10.1111\/acer.14259","archive":["Portico"],"relation":{},"ISSN":["0145-6008","1530-0277"],"issn-type":[{"value":"0145-6008","type":"print"},{"value":"1530-0277","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,25]]},"assertion":[{"value":"2019-06-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}