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Author:
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Pérez Martín, Margarita; Rivera, Patricia; Blanco Calvo, Eduardo; Lorefice, Clara; Decara, Juan; Pavón, Francisco Javier; Serrano, Antonia; Rodríguez de Fonseca, Fernando; Suárez, Juan
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Notes:
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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.
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) |
