title: Neuropeptide Y stimulates autophagy in hypothalamic neurons.
abstract: Aging is characterized by autophagy impairment that contributes to age-related disease aggravation. Moreover, it was described that the hypothalamus is a critical brain area for whole-body aging development and has impact on lifespan. Neuropeptide Y (NPY) is one of the major neuropeptides present in the hypothalamus, and it has been shown that, in aged animals, the hypothalamic NPY levels decrease. Because caloric restriction (CR) delays aging, at least in part, by stimulating autophagy, and also increases hypothalamic NPY levels, we hypothesized that NPY could have a relevant role on autophagy modulation in the hypothalamus. Therefore, the aim of this study was to investigate the role of NPY on autophagy in the hypothalamus. Using both hypothalamic neuronal in vitro models and mice overexpressing NPY in the hypothalamus, we observed that NPY stimulates autophagy in the hypothalamus. Mechanistically, in rodent hypothalamic neurons, NPY increases autophagy through the activation of NPY Y1 and Y5 receptors, and this effect is tightly associated with the concerted activation of PI3K, MEK/ERK, and PKA signaling pathways. Modulation of hypothalamic NPY levels may be considered a potential strategy to produce protective effects against hypothalamic impairments associated with age and to delay aging.
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal;
authors.forename: Célia A
authors.initials: CA
authors.lastname: Aveleira
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; and.
authors.forename: Mariana
authors.initials: M
authors.lastname: Botelho
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; and.
authors.forename: Sara
authors.initials: S
authors.lastname: Carmo-Silva
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal;
authors.forename: Jorge F
authors.identifier: http://orcid.org/0000-0003-0013-3711
authors.initials: JF
authors.lastname: Pascoal
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal;
authors.forename: Marisa
authors.initials: M
authors.lastname: Ferreira-Marques
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal;
authors.forename: Clévio
authors.initials: C
authors.lastname: Nóbrega
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal;
authors.forename: Luísa
authors.initials: L
authors.lastname: Cortes
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal;
authors.forename: Jorge
authors.initials: J
authors.lastname: Valero
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal;
authors.forename: Lígia
authors.initials: L
authors.lastname: Sousa-Ferreira
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal;
authors.forename: Ana R
authors.initials: AR
authors.lastname: Álvaro
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal;
authors.forename: Magda
authors.initials: M
authors.lastname: Santana
authors.affiliation: Center of Molecular Physiology of the Brain, Department of Neurology, University Medicine Göttingen, 37073 Göttingen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kügler
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; and.
authors.forename: Luís
authors.initials: L
authors.lastname: Pereira de Almeida
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; and ccavadas@uc.pt.
authors.forename: Cláudia
authors.identifier: http://orcid.org/0000-0001-8020-9266
authors.initials: C
authors.lastname: Cavadas
mesh_terms: D000375:Aging; D000818:Animals; D001343:Autophagy; D001921:Brain / Q000378:metabolism; D031204:Caloric Restriction; D005260:Female; D007031:Hypothalamus / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology*; D009478:Neuropeptide Y / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D009478:Neuropeptide Y
keywords: aging; autophagy; hypothalamus; neuropeptide Y