title: Evidence that activation of nuclear peroxisome proliferator-activated receptor alpha (PPARα) modulates sleep homeostasis in rats.
abstract: The peroxisome proliferator-activated receptor alpha (PPARα) is a member of the nuclear receptor superfamily that has been suggested as a modulator of several physiological functions. The PPARα recognizes as an endogenous ligand the anorexic lipid mediator oleoylethanolamide (OEA) which displays wake-inducing properties. Despite that recent evidence indicates that activation of PPARα by synthetic agonists such as Wy14643 enhances waking as well as the extracellular contents of wake-related neurotransmitters, the role of PPARα in sleep recovery after prolonged waking has not been fully described. Thus, the aim of this study was to characterize if PPARα regulates sleep rebound after total sleep deprivation (TSD). We report that after 6h of TSD activation of PPARα by pharmacological systemic administration of OEA (10, 20 or 30mg/Kg, i.p.) promoted alertness by blocking the sleep rebound after TSD. Besides, wake-linked compounds such as dopamine, norepinephrine, serotonin, or adenosine collected from nucleus accumbens were enhanced after TSD in OEA-treated animals. These sleep and neurochemical results were mimicked after injection of PPARα agonist Wy14643 (10, 20, 30mg/Kg, i.p.). However, similar findings from the sham of vehicle groups were observed if PPARα antagonist MK-886 was administered to rats (10, 20, 30mg/Kg, i.p.). Our results strengthened the hypothesis that PPARα might modulate sleep and neurochemical homeostasis after sleep deprivation.
authors.affiliation: Laboratorio de Neurociencias Moleculares e Integrativas, Escuela de Medicina, División Ciencias de la Salud, Universidad Anáhuac Mayab, Mérida, Yucatán, México; Grupo de Investigación en Envejecimiento, División Ciencias de la Salud, Universidad Anáhuac Mayab, Mérida, Yucatán, México; Grupo de Investigación Desarrollos Tecnológicos para la Salud, División de Ingeniería y Ciencias Exactas, Universidad Anáhuac Mayab, Mérida, Yucatán, México; Intercontinental Neuroscience Research Group, México. Electronic address: eric.murillo@anahuac.mx.
authors.forename: Eric
authors.initials: E
authors.lastname: Murillo-Rodríguez
authors.affiliation: Departamento de Neuropatología Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D.F., México.
authors.forename: Khalil
authors.initials: K
authors.lastname: Guzmán
authors.affiliation: Centro de Investigaciones Regionales "Dr. Hideyo Noguchi", Universidad Autónoma de Yucatán. Mérida, Yucatán. México.
authors.forename: Gloria
authors.initials: G
authors.lastname: Arankowsky-Sandoval
authors.affiliation: Laboratorio de Neurociencias Moleculares e Integrativas, Escuela de Medicina, División Ciencias de la Salud, Universidad Anáhuac Mayab, Mérida, Yucatán, México; Grupo de Investigación en Envejecimiento, División Ciencias de la Salud, Universidad Anáhuac Mayab, Mérida, Yucatán, México.
authors.forename: Mireille
authors.initials: M
authors.lastname: Salas-Crisóstomo
authors.affiliation: Laboratorio de Neurociencias Moleculares e Integrativas, Escuela de Medicina, División Ciencias de la Salud, Universidad Anáhuac Mayab, Mérida, Yucatán, México; Grupo de Investigación en Envejecimiento, División Ciencias de la Salud, Universidad Anáhuac Mayab, Mérida, Yucatán, México.
authors.forename: Ramsés
authors.initials: R
authors.lastname: Jiménez-Moreno
authors.affiliation: Intercontinental Neuroscience Research Group, México; Unidad de Trastornos del Movimiento y Sueño (TMS), Hospital General "Dr. Manuel Gea González", México, D.F., México.
authors.forename: Oscar
authors.initials: O
authors.lastname: Arias-Carrión
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009829:Oleic Acids / Q000494:pharmacology; D047493:PPAR alpha / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D012892:Sleep Deprivation / Q000378:metabolism; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology; D064690:Wakefulness-Promoting Agents / Q000494:pharmacology*; D002722:Chlorobenzenes
chemical_list: D000241:Adenosine; D015306:Biogenic Monoamines; D063388:Endocannabinoids; D007211:Indoles; D009829:Oleic Acids; D047493:PPAR alpha; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D064690:Wakefulness-Promoting Agents; C060893:MK-886; D002722:Chlorobenzenes; C488250:oleoylethanolamide; C006253:pirinixic acid
keywords: Adenosine; HPLC; Microdialysis; Serotonin; Sleep deprivation; Waking