RT Journal Article T1 Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches. A1 Perez-Martin, Margarita A1 Rivera, Patricia A1 Blanco, Eduardo A1 Lorefice, Clara A1 Decara, Juan A1 Pavon, Francisco J A1 Serrano, Antonia A1 Rodriguez-de-Fonseca, Fernando A1 Suarez, Juan K1 PPARα K1 Aging K1 Environment K1 Hippocampus K1 Neurogenesis K1 Subventricular zone AB 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. PB Frontiers Research Foundation SN 1662-4548 YR 2016 FD 2016-03-09 LK http://hdl.handle.net/10668/9945 UL http://hdl.handle.net/10668/9945 LA en NO Pérez-Martín M, Rivera P, Blanco E, Lorefice C, Decara J, Pavón FJ, et al. Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches. Front Neurosci. 2016 Mar 9;10:89 NO 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 contractsfrom the National System of Health, ISCIII (grant numbers: CP12/03109, CP14/00212 and CP14/00173, respectively). DS RISalud RD Apr 11, 2025