Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain

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dc.contributor.authorBlanco Calvo, Eduardo
dc.contributor.authorRodríguez de Fonseca, Fernando
dc.contributor.authorRivera, Patricia
dc.contributor.authorSuárez, Juan
dc.contributor.authorBindila, Laura
dc.contributor.authorAlén, Francisco
dc.contributor.authorRubio, Leticia
dc.contributor.authorVargas, Antonio
dc.contributor.authorPavón, Francisco Javier
dc.contributor.authorSerrano, Antonia
dc.contributor.authorLutz, Beat
dc.date.accessioned2015-11-04T11:15:08Z
dc.date.available2015-11-04T11:15:08Z
dc.date.issued2015
dc.description.abstractChronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence.ca_ES
dc.description.sponsorshipGrant sponsor: 7th Framework Programme of European Union. Grant number: HEALTH-F2-2008-223713, REPROBESITY to FR and BL. Grant sponsor: Ministerio de Ciencia e Innovación. Grant numbers: SAF2010-19087 and SAF 2010-20521 to FR. Grant sponsor: Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad (MINECO), UE-ERDF. Grant number: CP12/03109 to JS. Grant sponsor: Red de Trastornos Adictivos, ISCIII, MINECO. Grant number: RD12/0028/0001 to FR. Grant sponsor: Plan Nacional Sobre Drogas, Ministerio de Sanidad y Consumo. Grant number: PNSD2010/143 to JS. Grant sponsor: Consejería de Economía, Innovación y Ciencia, Junta de Andalucía, UE/ERDF. Grant numbers: PI45403 and CTS-8221 to FR. Grant sponsor: Consejería de Salud, Junta de Andalucía, UE/ERDF. Grant numbers: SAS111224 to JS. Grant sponsor: German Research Foundation DFG. Grant number: FOR926, project CP to BL. JS, FP, and AS hold “Miguel Servet” research contracts from the National System of Health, ISCIII (grant numbers: CP12/03109, CP14/00212 and CP14/00173, respectively).
dc.identifier.doihttps://doi.org/10.3389/fncel.2015.00379
dc.identifier.idgrec023723
dc.identifier.issn1662-5102
dc.identifier.urihttp://hdl.handle.net/10459.1/48916
dc.language.isoengca_ES
dc.publisherFrontiersca_ES
dc.relationMICINN/PN2008-2011/SAF2010-19087
dc.relationMICINN/PN2008-2011/SAF2010-20521
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.3389/fncel.2015.00379ca_ES
dc.relation.ispartofCellular Neuroscience, 2015, vol. 9, núm. 379, p. 1-14ca_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/223713
dc.rightscc-by (c) Rodríguez de Fonseca, Fernando et al., 2015ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subjectAlcoholca_ES
dc.subjectACEAca_ES
dc.subjectJWH133ca_ES
dc.titlePharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brainca_ES
dc.typearticleca_ES
dc.type.versionpublishedVersionca_ES
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