Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches

Peroxisome proliferator-activated receptor alpha (PPARα) ligands have been shown to modulate recovery after brain insults such as ischemia and irradiation by enhancing neurogenesis. In the present study, we investigated the effect of the genetic deletion of PPARα receptors on the proliferative rate...

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Autores: Pérez Martín, Margarita, Rivera, Patricia, Blanco Calvo, Eduardo, Lorefice, Clara, Decara, Juan, Pavón, Francisco Javier, Serrano, Antonia, Rodríguez de Fonseca, Fernando, Suárez, Juan
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/57238
Acceso en línea:https://doi.org/10.3389/fnins.2016.00089
http://hdl.handle.net/10459.1/57238
Access Level:acceso abierto
Palabra clave:Aging
Environment
PPARα
Subventricular zone
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spelling Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic NichesPérez Martín, MargaritaRivera, PatriciaBlanco Calvo, EduardoLorefice, ClaraDecara, JuanPavón, Francisco JavierSerrano, AntoniaRodríguez de Fonseca, FernandoSuárez, JuanAgingEnvironmentPPARαSubventricular zonePeroxisome proliferator-activated receptor alpha (PPARα) ligands have been shown to modulate recovery after brain insults such as ischemia and irradiation by enhancing neurogenesis. In the present study, we investigated the effect of the genetic deletion of PPARα receptors on the proliferative rate of neural precursor cells (NPC) in the adult brain. The study was performed in aged Pparα −/− mice exposed to nutritional (treats) and environmental (games) enrichments for 20 days. We performed immunohistochemical analyses of cells containing the replicating cell DNA marker 5-bromo-2′ -deoxyuridine (BrdU+) and the immature neuronal marker doublecortin (Dcx+) in the main neurogenic zones of the adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ), and/or hypothalamus. Results indicated a reduction in the number of BrdU+ cells in the neurogenic zones analyzed as well as Dcx+ cells in the SGZ during aging (2, 6, and 18 months). Pparα deficiency alleviated the age-related reduction of NPC proliferation (BrdU+ cells) in the SVZ of the 18-months-old mice. While no genotype effect on NPC proliferation was detected in the SGZ during aging, an accentuated reduction in the number of Dcx+ cells was observed in the SGZ of the 6-months-old Pparα −/− mice. Exposing the 18-months-old mice to nutritional and environmental enrichments reversed the Pparα −/−-induced impairment of NPC proliferation in the neurogenic zones analyzed. The enriched environment did not modify the number of SGZ Dcx+ cells in the 18 months old Pparα −/− mice. These results identify PPARα receptors as a potential target to counteract the naturally observed decline in adult NPC proliferation associated with aging and impoverished environments.Grant sponsor: 7th Framework Programme of European Union. Grant number: HEALTH-F2-2008-223713, REPROBESITY to FR. Grant sponsor: Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad (MINECO), UEERDF. Grant numbers: PI13/02261 to FR. and 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 and PNSD2015/047 to JS. Grant sponsor: Fundació La Marató de TV3. Grant number: 386/C/2011. 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 number: SAS111224 to FR. 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)Frontiers Media2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.3389/fnins.2016.00089http://hdl.handle.net/10459.1/57238reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL)InglésReproducció del document publicat a https://doi.org/10.3389/fnins.2016.00089Frontiers in Neuroscience, 2016, vol. 10, núm. 89, p. 1-12info:eu-repo/grantAgreement/EC/FP7/223713cc-by, (c) Pérez-Martín et al., 2016info:eu-repo/semantics/openAccessoai:repositori.udl.cat:10459.1/572382026-06-24T12:42:17Z
dc.title.none.fl_str_mv Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches
title Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches
spellingShingle Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches
Pérez Martín, Margarita
Aging
Environment
PPARα
Subventricular zone
title_short Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches
title_full Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches
title_fullStr Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches
title_full_unstemmed Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches
title_sort Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches
dc.creator.none.fl_str_mv Pérez Martín, Margarita
Rivera, Patricia
Blanco Calvo, Eduardo
Lorefice, Clara
Decara, Juan
Pavón, Francisco Javier
Serrano, Antonia
Rodríguez de Fonseca, Fernando
Suárez, Juan
author Pérez Martín, Margarita
author_facet Pérez Martín, Margarita
Rivera, Patricia
Blanco Calvo, Eduardo
Lorefice, Clara
Decara, Juan
Pavón, Francisco Javier
Serrano, Antonia
Rodríguez de Fonseca, Fernando
Suárez, Juan
author_role author
author2 Rivera, Patricia
Blanco Calvo, Eduardo
Lorefice, Clara
Decara, Juan
Pavón, Francisco Javier
Serrano, Antonia
Rodríguez de Fonseca, Fernando
Suárez, Juan
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Aging
Environment
PPARα
Subventricular zone
topic Aging
Environment
PPARα
Subventricular zone
description Peroxisome proliferator-activated receptor alpha (PPARα) ligands have been shown to modulate recovery after brain insults such as ischemia and irradiation by enhancing neurogenesis. In the present study, we investigated the effect of the genetic deletion of PPARα receptors on the proliferative rate of neural precursor cells (NPC) in the adult brain. The study was performed in aged Pparα −/− mice exposed to nutritional (treats) and environmental (games) enrichments for 20 days. We performed immunohistochemical analyses of cells containing the replicating cell DNA marker 5-bromo-2′ -deoxyuridine (BrdU+) and the immature neuronal marker doublecortin (Dcx+) in the main neurogenic zones of the adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ), and/or hypothalamus. Results indicated a reduction in the number of BrdU+ cells in the neurogenic zones analyzed as well as Dcx+ cells in the SGZ during aging (2, 6, and 18 months). Pparα deficiency alleviated the age-related reduction of NPC proliferation (BrdU+ cells) in the SVZ of the 18-months-old mice. While no genotype effect on NPC proliferation was detected in the SGZ during aging, an accentuated reduction in the number of Dcx+ cells was observed in the SGZ of the 6-months-old Pparα −/− mice. Exposing the 18-months-old mice to nutritional and environmental enrichments reversed the Pparα −/−-induced impairment of NPC proliferation in the neurogenic zones analyzed. The enriched environment did not modify the number of SGZ Dcx+ cells in the 18 months old Pparα −/− mice. These results identify PPARα receptors as a potential target to counteract the naturally observed decline in adult NPC proliferation associated with aging and impoverished environments.
publishDate 2016
dc.date.none.fl_str_mv 2016
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/fnins.2016.00089
http://hdl.handle.net/10459.1/57238
url https://doi.org/10.3389/fnins.2016.00089
http://hdl.handle.net/10459.1/57238
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a https://doi.org/10.3389/fnins.2016.00089
Frontiers in Neuroscience, 2016, vol. 10, núm. 89, p. 1-12
info:eu-repo/grantAgreement/EC/FP7/223713
dc.rights.none.fl_str_mv cc-by, (c) Pérez-Martín et al., 2016
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by, (c) Pérez-Martín et al., 2016
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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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