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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Main Authors: Margarita ePerez-Martin, Patricia eRivera, Eduardo eBlanco, Clara eLorefice, Juan eDecara, FRANCISCO JAVIER ePAVON, Antonia eSerrano, FERNANDO eRODRIGUEZ DE FONSECA, JUAN eSUAREZ
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-03-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00089/full
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author Margarita ePerez-Martin
Patricia eRivera
Eduardo eBlanco
Clara eLorefice
Juan eDecara
FRANCISCO JAVIER ePAVON
Antonia eSerrano
FERNANDO eRODRIGUEZ DE FONSECA
JUAN eSUAREZ
author_facet Margarita ePerez-Martin
Patricia eRivera
Eduardo eBlanco
Clara eLorefice
Juan eDecara
FRANCISCO JAVIER ePAVON
Antonia eSerrano
FERNANDO eRODRIGUEZ DE FONSECA
JUAN eSUAREZ
author_sort Margarita ePerez-Martin
collection DOAJ
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, 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.
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spelling doaj.art-d1c1d37c54cb40fabfa799500ea73e352022-12-22T02:45:39ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2016-03-011010.3389/fnins.2016.00089177411Environmental enrichment, age and PPARα interact to regulate proliferation in neurogenic nichesMargarita ePerez-Martin0Patricia eRivera1Eduardo eBlanco2Clara eLorefice3Juan eDecara4FRANCISCO JAVIER ePAVON5Antonia eSerrano6FERNANDO eRODRIGUEZ DE FONSECA7JUAN eSUAREZ8Universidad de MálagaInstituto de Investigación Biomédica de Málaga. Hospital Regional Universitario de MálagaUniversitat de LleidaInstituto de Investigación Biomédica de Málaga. Hospital Regional Universitario de MálagaInstituto de Investigación Biomédica de Málaga. Hospital Regional Universitario de MálagaInstituto de Investigación Biomédica de Málaga. Hospital Regional Universitario de MálagaInstituto de Investigación Biomédica de Málaga. Hospital Regional Universitario de MálagaInstituto de Investigación Biomédica de Málaga. Hospital Regional Universitario de MálagaInstituto de Investigación Biomédica de Málaga. Hospital Regional Universitario de MálagaPeroxisome 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, 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.http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00089/fullAgingHippocampusNeurogenesisenvironmentSubventricular zonePPARα
spellingShingle Margarita ePerez-Martin
Patricia eRivera
Eduardo eBlanco
Clara eLorefice
Juan eDecara
FRANCISCO JAVIER ePAVON
Antonia eSerrano
FERNANDO eRODRIGUEZ DE FONSECA
JUAN eSUAREZ
Environmental enrichment, age and PPARα interact to regulate proliferation in neurogenic niches
Frontiers in Neuroscience
Aging
Hippocampus
Neurogenesis
environment
Subventricular zone
PPARα
title 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_short 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
topic Aging
Hippocampus
Neurogenesis
environment
Subventricular zone
PPARα
url http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00089/full
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