{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T09:15:35Z","timestamp":1769505335127,"version":"3.49.0"},"reference-count":75,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The European Foundation for Alcohol Research","award":["IT1512-22"],"award-info":[{"award-number":["IT1512-22"]}]},{"name":"The European Foundation for Alcohol Research","award":["FP7-PEOPLE- 2013-CIG #618807"],"award-info":[{"award-number":["FP7-PEOPLE- 2013-CIG #618807"]}]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM)","award":["IT1512-22"],"award-info":[{"award-number":["IT1512-22"]}]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM)","award":["FP7-PEOPLE- 2013-CIG #618807"],"award-info":[{"award-number":["FP7-PEOPLE- 2013-CIG #618807"]}]},{"DOI":"10.13039\/501100003086","name":"Basque Government","doi-asserted-by":"publisher","award":["IT1512-22"],"award-info":[{"award-number":["IT1512-22"]}],"id":[{"id":"10.13039\/501100003086","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003086","name":"Basque Government","doi-asserted-by":"publisher","award":["FP7-PEOPLE- 2013-CIG #618807"],"award-info":[{"award-number":["FP7-PEOPLE- 2013-CIG #618807"]}],"id":[{"id":"10.13039\/501100003086","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundaci\u00f3n Vital","award":["IT1512-22"],"award-info":[{"award-number":["IT1512-22"]}]},{"name":"Fundaci\u00f3n Vital","award":["FP7-PEOPLE- 2013-CIG #618807"],"award-info":[{"award-number":["FP7-PEOPLE- 2013-CIG #618807"]}]},{"name":"FP7 Marie Curie Actions Career Integration","award":["IT1512-22"],"award-info":[{"award-number":["IT1512-22"]}]},{"name":"FP7 Marie Curie Actions Career Integration","award":["FP7-PEOPLE- 2013-CIG #618807"],"award-info":[{"award-number":["FP7-PEOPLE- 2013-CIG #618807"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Astrocytic-secreted matricellular proteins have been shown to influence various aspects of synaptic function. More recently, they have been found altered in animal models of psychiatric disorders such as drug addiction. Hevin (also known as Sparc-like 1) is a matricellular protein highly expressed in the adult brain that has been implicated in resilience to stress, suggesting a role in motivated behaviors. To address the possible role of hevin in drug addiction, we quantified its expression in human postmortem brains and in animal models of alcohol abuse. Hevin mRNA and protein expression were analyzed in the postmortem human brain of subjects with an antemortem diagnosis of alcohol use disorder (AUD, n = 25) and controls (n = 25). All the studied brain regions (prefrontal cortex, hippocampus, caudate nucleus and cerebellum) in AUD subjects showed an increase in hevin levels either at mRNA or\/and protein levels. To test if this alteration was the result of alcohol exposure or indicative of a susceptibility factor to alcohol consumption, mice were exposed to different regimens of intraperitoneal alcohol administration. Hevin protein expression was increased in the nucleus accumbens after withdrawal followed by a ethanol challenge. The role of hevin in AUD was determined using an RNA interference strategy to downregulate hevin expression in nucleus accumbens astrocytes, which led to increased ethanol consumption. Additionally, ethanol challenge after withdrawal increased hevin levels in blood plasma. Altogether, these results support a novel role for hevin in the neurobiology of AUD.<\/jats:p>","DOI":"10.3390\/biom13020234","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T01:30:30Z","timestamp":1674696630000},"page":"234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Matricellular Protein Hevin Is Involved in Alcohol Use Disorder"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1749-7055","authenticated-orcid":false,"given":"Amaia","family":"Nu\u00f1ez-delMoral","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of the Basque Country, UPV\/EHU, 48940 Leioa, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM), Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3412-4514","authenticated-orcid":false,"given":"Paula C.","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Universidade Federal de S\u00e3o Paulo-UNIFESP, S\u00e3o Paulo 04023-062, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iria","family":"Brocos-Mosquera","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of the Basque Country, UPV\/EHU, 48940 Leioa, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Augusto","family":"Anesio","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Universidade Federal de S\u00e3o Paulo-UNIFESP, S\u00e3o Paulo 04023-062, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9721-2867","authenticated-orcid":false,"given":"Paola","family":"Palombo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Universidade Federal de S\u00e3o Paulo-UNIFESP, S\u00e3o Paulo 04023-062, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8131-6108","authenticated-orcid":false,"given":"Rosana","family":"Camarini","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio C.","family":"Cruz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Universidade Federal de S\u00e3o Paulo-UNIFESP, S\u00e3o Paulo 04023-062, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9941-012X","authenticated-orcid":false,"given":"Luis F.","family":"Callado","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of the Basque Country, UPV\/EHU, 48940 Leioa, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM), Spain"},{"name":"Biocruces-Bizkaia Health Research Institute, 48903 Barakaldo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8212-751X","authenticated-orcid":false,"given":"Vincent","family":"Vialou","sequence":"additional","affiliation":[{"name":"Institute of Biology Paris Seine, Neuroscience Paris Seine, CNRS UMR8246, INSERM U1130, Sorbonne Universit\u00e9, 75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0207-9122","authenticated-orcid":false,"given":"Amaia M.","family":"Erdozain","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of the Basque Country, UPV\/EHU, 48940 Leioa, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental (CIBERSAM), Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1038\/s41386-020-00950-y","article-title":"Addiction as a brain disease revised: Why it still matters, and the need for consilience","volume":"46","author":"Heilig","year":"2021","journal-title":"Neuropsychopharmacology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1016\/S0140-6736(09)60746-7","article-title":"Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders","volume":"373","author":"Rehm","year":"2009","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1016\/S0140-6736(10)61462-6","article-title":"Drug harms in the UK: A multicriteria decision analysis","volume":"376","author":"Nutt","year":"2010","journal-title":"Lancet"},{"key":"ref_4","unstructured":"WHO (2018, September 27). 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