title: Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model.
abstract: The evidence for a protective role of physical activity on the risk and progression of Alzheimer's disease (AD) has been growing in the last years. Here we studied the influence of a prolonged physical and cognitive stimulation on neurodegeneration, with special emphasis on hippocampal neuron loss and associated behavioral impairment in the Tg4-42 mouse model of AD. Tg4-42 mice overexpress Aβ4-42 without any mutations, and develop an age-dependent hippocampal neuron loss associated with a severe memory decline. We demonstrate that long-term voluntary exercise diminishes CA1 neuron loss and completely rescues spatial memory deficits in different experimental settings. This was accompanied by changes in the gene expression profile of Tg4-42 mice. Deep sequencing analysis revealed an upregulation of chaperones involved in endoplasmatic reticulum protein processing, which might be intimately linked to the beneficial effects seen upon long-term exercise. We believe that we provide evidence for the first time that enhanced physical activity counteracts neuron loss and behavioral deficits in a transgenic AD mouse model. The present findings underscore the relevance of increased physical activity as a potential strategy in the prevention of dementia.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, Göttingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hüttenrauch
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, Göttingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Brauß
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, Göttingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kurdakova
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, Göttingen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Borgers
authors.affiliation: Department of Clinical Neurophysiology, University Medical Center (UMG), Georg-August-University, Göttingen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Klinker
authors.affiliation: Department of Clinical Neurophysiology, University Medical Center (UMG), Georg-August-University, Göttingen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Liebetanz
authors.affiliation: Department of Developmental Biochemistry, DNA Microarray and Deep-Sequencing Facility, University Medical Center (UMG), Georg-August-University, Göttingen, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Salinas-Riester
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, Göttingen, Germany.|German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Wiltfang
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, Göttingen, Germany.
authors.forename: H W
authors.initials: HW
authors.lastname: Klafki
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, Göttingen, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Wirths
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D006624:Hippocampus / Q000503:physiopathology*; D008569:Memory Disorders / Q000150:complications* / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000150:complications* / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D010805:Physical Conditioning, Animal; D060888:Real-Time Polymerase Chain Reaction