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

Chronic 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 C...

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Autores: Blanco Calvo, Eduardo, Rodríguez de Fonseca, Fernando, Rivera, Patricia, Suárez, Juan, Bindila, Laura, Alén, Francisco, Rubio, Leticia, Vargas, Antonio, Pavón, Francisco Javier, Serrano, Antonia, Lutz, Beat
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Recursos:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/48916
Acesso em linha:https://doi.org/10.3389/fncel.2015.00379
http://hdl.handle.net/10459.1/48916
Access Level:acceso abierto
Palavra-chave:Alcohol
ACEA
JWH133
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spelling Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brainBlanco Calvo, EduardoRodríguez de Fonseca, FernandoRivera, PatriciaSuárez, JuanBindila, LauraAlén, FranciscoRubio, LeticiaVargas, AntonioPavón, Francisco JavierSerrano, AntoniaLutz, BeatAlcoholACEAJWH133Chronic 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.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 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).Frontiers2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.3389/fncel.2015.00379http://hdl.handle.net/10459.1/48916reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL)InglésMICINN/PN2008-2011/SAF2010-19087MICINN/PN2008-2011/SAF2010-20521Reproducció del document publicat a https://doi.org/10.3389/fncel.2015.00379Cellular Neuroscience, 2015, vol. 9, núm. 379, p. 1-14info:eu-repo/grantAgreement/EC/FP7/223713cc-by (c) Rodríguez de Fonseca, Fernando et al., 2015info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/oai:repositori.udl.cat:10459.1/489162026-06-24T12:42:17Z
dc.title.none.fl_str_mv Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain
title Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain
spellingShingle Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain
Blanco Calvo, Eduardo
Alcohol
ACEA
JWH133
title_short Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain
title_full Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain
title_fullStr Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain
title_full_unstemmed Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain
title_sort Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain
dc.creator.none.fl_str_mv Blanco Calvo, Eduardo
Rodríguez de Fonseca, Fernando
Rivera, Patricia
Suárez, Juan
Bindila, Laura
Alén, Francisco
Rubio, Leticia
Vargas, Antonio
Pavón, Francisco Javier
Serrano, Antonia
Lutz, Beat
author Blanco Calvo, Eduardo
author_facet Blanco Calvo, Eduardo
Rodríguez de Fonseca, Fernando
Rivera, Patricia
Suárez, Juan
Bindila, Laura
Alén, Francisco
Rubio, Leticia
Vargas, Antonio
Pavón, Francisco Javier
Serrano, Antonia
Lutz, Beat
author_role author
author2 Rodríguez de Fonseca, Fernando
Rivera, Patricia
Suárez, Juan
Bindila, Laura
Alén, Francisco
Rubio, Leticia
Vargas, Antonio
Pavón, Francisco Javier
Serrano, Antonia
Lutz, Beat
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alcohol
ACEA
JWH133
topic Alcohol
ACEA
JWH133
description Chronic 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.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.3389/fncel.2015.00379
http://hdl.handle.net/10459.1/48916
url https://doi.org/10.3389/fncel.2015.00379
http://hdl.handle.net/10459.1/48916
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv MICINN/PN2008-2011/SAF2010-19087
MICINN/PN2008-2011/SAF2010-20521
Reproducció del document publicat a https://doi.org/10.3389/fncel.2015.00379
Cellular Neuroscience, 2015, vol. 9, núm. 379, p. 1-14
info:eu-repo/grantAgreement/EC/FP7/223713
dc.rights.none.fl_str_mv cc-by (c) Rodríguez de Fonseca, Fernando et al., 2015
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
rights_invalid_str_mv cc-by (c) Rodríguez de Fonseca, Fernando et al., 2015
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:Repositori Obert UdL
instname:Universitat de Lleida (UdL)
instname_str Universitat de Lleida (UdL)
reponame_str Repositori Obert UdL
collection Repositori Obert UdL
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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