Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context.

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• dc.contributor.author Rivera, Patriciaca
• dc.contributor.author Bindila, Lauraca
• dc.contributor.author Pastor, Antonioca
• dc.contributor.author Pérez Martín, Margaritaca
• dc.contributor.author Pavón, Francisco Javierca
• dc.contributor.author Serrano, Antoniaca
• dc.contributor.author Torre Fornell, Rafael de laca
• dc.contributor.author Lutz, Beatca
• dc.contributor.author Rodríguez de Fonseca, Fernandoca
• dc.contributor.author Suárez, Juanca
• dc.date.accessioned 2015-06-12T07:39:38Z
• dc.date.available 2015-06-12T07:39:38Z
• dc.date.issued 2015
• dc.description.abstract Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study. Cell proliferation (phospho-H3(+) or BrdU(+) cells) of the main adult neurogenic zones as well as apoptosis (cleaved caspase-3(+)), astroglia (GFAP(+)), and microglia (Iba1(+) cells) were analyzed in the hippocampus, hypothalamus and striatum of rats intraperitoneally treated with URB597 (0.3 mg/kg/day) at one dose/4-days resting or 5 doses (1 dose/day). Repeated URB597 treatment increased the plasma levels of the N-acylethanolamines oleoylethanolamide, palmitoylethanolamide and arachidonoylethanolamine, reduced the plasma levels of glucose, triglycerides and cholesterol, and induced a transitory body weight decrease. The hippocampi of repeated URB597-treated rats showed a reduced number of phospho-H3(+) and BrdU(+) subgranular cells as well as GFAP(+), Iba1(+) and cleaved caspase-3(+) cells, which was accompanied with decreased hippocampal expression of the cannabinoid CB1 receptor gene Cnr1 and Faah. In the hypothalami of these rats, the number of phospho-H3(+), GFAP(+) and 3-weeks-old BrdU(+) cells was specifically decreased. The reduced striatal expression of CB1 receptor in repeated URB597-treated rats was only associated with a reduced apoptosis. In contrast, the striatum of acute URB597-treated rats showed an increased number of subventricular proliferative, astroglial and apoptotic cells, which was accompanied with increased Faah expression. Main results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia and apoptosis in a brain region-dependent manner, which were coupled to local changes in Faah and/or Cnr1 expression and a negative energy context.ca
• dc.description.sponsorship Grant 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, SAF 2010-20521; Grant sponsor: Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, UE-ERDF; Grant number: CP12/03109; Grant sponsor: Red de Trastornos Adictivos; Grant numbers: RD12/0028/0001, RD12/0028/0009; Grant sponsor: CIBERobn; Grant sponsor: Plan Nacional Sobre Drogas, Ministerio de Sanidad y Consumo; Grant number: PNSD2010/143; Grant sponsor: Consejería de Economía, Innovación y Ciencia, Junta de Andalucía, UE/ERDF; Grant numbers: CTS-433, P-11-CVI-07637; Grant sponsor: Consejería de Salud, Junta de Andalucía; Grant numbers: PI0232/2008, PI0029/2008, SAS111224; Grant sponsor: Fundació La Marató de TV3; Grant number: 386/C/2011; Grant sponsor: German Research Foundation DFG; Grant number: FOR629, project CP2 to BL. JS, FP, and AS hold “Miguel Servet” research contracts from the National System of Health, ISCIII (Grant numbers: CP12/03109, CP14/00212, CP14/00173 respectively).
• dc.format.mimetype application/pdfca
• dc.identifier.citation Rivera P, Bindila L, Pastor A, Pérez-Martín M, Pavón FJ, Serrano A. et al. Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context. Front Cell Neurosci. 2015 Mar 27;9:98. DOI: 10.3389/fncel.2015.00098. eCollection 2015.ca
• dc.identifier.doi http://dx.doi.org/10.3389/fncel.2015.00098
• dc.identifier.issn 1662-5102
• dc.identifier.uri http://hdl.handle.net/10230/23804
• dc.language.iso engca
• dc.publisher Frontiersca
• dc.relation.ispartof Frontiers in Cellular Neuroscience. 2015 Mar 27;9:98
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/223713
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2010-19087
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2010-20521
• dc.rights © 2015 Rivera, Bindila, Pastor, Pérez-Martín, Pavón, Serrano, de la Torre, Lutz, Rodríguez de Fonseca and Suárez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).https://creativecommons.org/licenses/by/4.0/. The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/ca
• dc.subject.other Neurobiologia del desenvolupamentca
• dc.subject.other Cannabinoidesca
• dc.title Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context.ca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersion