title: Oxidative Stress Is a Central Target for Physical Exercise Neuroprotection Against Pathological Brain Aging.
abstract: Physical exercise is suggested for preventing or delaying senescence and Alzheimer's disease (AD). We have examined its therapeutic value in the advanced stage of AD-like pathology in 3xTg-AD female mice through voluntary wheel running from 12 to 15 months of age. Mice submitted to exercise showed improved body fitness, immunorejuvenation, improvement of behavior and cognition, and reduced amyloid and tau pathology. Brain tissue analysis of aged 3xTg-AD mice showed high levels of oxidative damage. However, this damage was decreased by physical exercise through regulation of redox homeostasis. Network analyses showed that oxidative stress was a central event, which correlated with AD-like pathology and the AD-related behaviors of anxiety, apathy, and cognitive loss. This study corroborates the importance of redox mechanisms in the neuroprotective effect of physical exercise, and supports the theory of the crucial role of oxidative stress in the switch from normal brain aging to pathological aging and AD.
authors.affiliation: Institut d'Investigacions Biomèdiques de Barcelona - CSIC, Spain. Present address: Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Yoelvis
authors.initials: Y
authors.lastname: García-Mesa
authors.affiliation: Signalling and Cell Cycle Laboratory, Institute for Research in Biomedicine, Barcelona, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Colie
authors.affiliation: Institut d'Investigacions Biomèdiques de Barcelona - CSIC, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Corpas
authors.affiliation: Institut d'Investigacions Biomèdiques de Barcelona - CSIC, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Cristòfol
authors.affiliation: Department of Applied Mathematics IV, Universitat Politècnica de Catalunya, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Comellas
authors.affiliation: Signalling and Cell Cycle Laboratory, Institute for Research in Biomedicine, Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.
authors.forename: Angel R
authors.initials: AR
authors.lastname: Nebreda
authors.affiliation: Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, Institute of Neuroscience, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Lydia
authors.initials: L
authors.lastname: Giménez-Llort
authors.affiliation: Institut d'Investigacions Biomèdiques de Barcelona - CSIC, Spain. Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain. coral.sanfeliu@iibb.csic.es.
authors.forename: Coral
authors.initials: C
authors.lastname: Sanfeliu
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control / Q000523:psychology; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016922:Cellular Senescence / Q000502:physiology*; D003071:Cognition / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology*; D000066829:Neuroprotection / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000379:methods / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D000682:Amyloid; D016875:tau Proteins
keywords: 3xTg-AD mice; Alzheimer’s disease; Amyloid βPhospho-tau.; Behavior tests; Cognition; Oxidative stress; Physical exercise