title: Memantine prevents reference and working memory impairment caused by sleep deprivation in both young and aged Octodon degus.
abstract: Memory loss is one of the key features of cognitive impairment in either aging, Mild Cognitive Impairment (MCI) or dementia. Pharmacological treatments for memory loss are today focused on addressing symptomatology. One of these approved compounds is memantine, a partial NMDA receptor antagonist that has proved its beneficial effects in cognition. The Octodon degus (O. degus) has been recently proposed as a potential model relevant for neurodegenerative diseases. However, there are no previous studies investigating the effect of pharmacological treatments for age-related cognitive impairment in this rodent. In this work we aimed to evaluate the effect of memantine on sleep deprivation (SD)-induced memory impairment in young and old O. degus. Young and old animals were trained in different behavioral paradigms validated for memory evaluation, and randomly assigned to a control (CTL, n=14) or an SD (n=14) condition, and treated with vehicle or memantine (10-mg/Kg i.p.) before the SD started. We demonstrate that SD impairs memory in both young and old animals, although the effect in the old group was significantly more severe (P<0.05). Memantine pretreatment was able to prevent the cognitive impairment caused by SD in both age groups, while it had no negative effect on CTL animals. The positive effect of memantine in counteracting the negative effect of SD on the retrieval process even in the aged O. degus further supports the translational potential of both the challenge and the species, and will enable a better understanding of the behavioral features of memantine effects, especially related with reference and working memories.
authors.affiliation: Clinical & Experimental Neuroscience (NiCE) and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Universitat Jaume I, 12071 Castellon, Spain; School of Medicine, Campus Mare Nostrum, University of Murcia, 30100 Murcia, Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Tarragon
authors.affiliation: School of Medicine, Campus Mare Nostrum, University of Murcia, 30100 Murcia, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Lopez
authors.affiliation: School of Medicine, Campus Mare Nostrum, University of Murcia, 30100 Murcia, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Estrada
authors.affiliation: School of Medicine, Campus Mare Nostrum, University of Murcia, 30100 Murcia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Gonzalez-Cuello
authors.affiliation: Clinical & Experimental Neuroscience (NiCE) and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Universitat Jaume I, 12071 Castellon, Spain; School of Medicine, Campus Mare Nostrum, University of Murcia, 30100 Murcia, Spain.
authors.forename: Carmen Ma
authors.initials: CM
authors.lastname: Ros
authors.affiliation: UCB Pharma S.A., Neuroscience Therapeutic Area, Chemin du Foriest, B-1420 Braine l'Alleud, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Lamberty
authors.affiliation: UMR 7179 Centre National de la Recherche Scientifique/Muséum National d'Histoire Naturelle, Brunoy, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Pifferi
authors.affiliation: GlaxoSmithKline, Clinical Pharmacology, Modeling & Simulation, Stockley Park, London UB11 1BT, United Kingdom.
authors.forename: Massimo
authors.initials: M
authors.lastname: Cella
authors.affiliation: Laboratory of Pharmacodynamics and Pharmacokinetics, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milan, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Canovi
authors.affiliation: Laboratory of Pharmacodynamics and Pharmacokinetics, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milan, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Guiso
authors.affiliation: Laboratory of Pharmacodynamics and Pharmacokinetics, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
authors.affiliation: School of Medicine, Campus Mare Nostrum, University of Murcia, 30100 Murcia, Spain.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Fernández-Villalba
authors.affiliation: Department of Pharmacology, Aix-Marseille University, Marseille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Blin
authors.affiliation: Department of Medical Pharmacology, University Lille-North, 1 Place Verdun, 59045 Lille, France.
authors.forename: Regis
authors.initials: R
authors.lastname: Bordet
authors.affiliation: GlaxoSmithKline R&D, Neurosciences Therapeutic Area, Gunnels Wood Road, Stevenage, Herts SG1 2NY, United Kingdom.
authors.forename: Jill C
authors.initials: JC
authors.lastname: Richardson
authors.affiliation: Clinical & Experimental Neuroscience (NiCE) and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Universitat Jaume I, 12071 Castellon, Spain; School of Medicine, Campus Mare Nostrum, University of Murcia, 30100 Murcia, Spain. Electronic address: ezquerro@uji.es.
authors.forename: María Trinidad
authors.initials: MT
authors.lastname: Herrero
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D005260:Female; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008559:Memantine / Q000097:blood / Q000494:pharmacology*; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008570:Memory, Short-Term / Q000187:drug effects* / Q000502:physiology; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000097:blood / Q000494:pharmacology*; D046329:Octodon; D011897:Random Allocation; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D012892:Sleep Deprivation / Q000150:complications* / Q000503:physiopathology
chemical_list: D018697:Nootropic Agents; D008559:Memantine
keywords: Alzheimer disease; Memantine; Memory; Octodon degus; Sleep deprivation