title: A Comparative Study Evaluating the Impact of Physical Exercise on Disease Progression in a Mouse Model of Alzheimer's Disease.
abstract: Evidence suggests that physical exercise can serve as a preventive strategy against Alzheimer's disease (AD). In contrast, much less is known about the impact of exercise when it is introduced after cognitive deficits are established. Using the TgCRND8 mouse model of amyloidosis, we compared the effects of exercise as an intervention strategy aimed at altering disease progression. Voluntary running for 1 month or 2 months was introduced in 3-month-old TgCRND8 mice, which exhibit amyloid-beta (Aβ) plaque pathology and cognitive deficits at this age. Specifically, we examined Aβ plaque load, spatial memory, and neurogenesis in the dentate gyrus in the hippocampus. After 1 month of running, TgCRND8 mice spent more time in the novel arm of the Y-maze compared to the familiar arms, indicating improved memory. The levels of doublecortin (a marker of immature neurons) were increased in TgCRND8 mice running for 1 month, but with no significant difference in the number of new mature neurons or plaque burden. As the disease progressed, running prevented further deficits in the Y-maze performance and hippocampal neurogenesis and it reduced plaque load pathology in TgCRND8 mice running for 2 months, compared to non-running transgenics. Therefore, the impact of running on memory, neurogenesis, and amyloid pathology was of greater significance when sustained through later stages of the disease.
authors.affiliation: Hurvitz Brain Sciences Program, Biological Sciences, Sunnybrook Research Institute, Toronto ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto ON, Canada.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Maliszewska-Cyna
authors.affiliation: Hurvitz Brain Sciences Program, Biological Sciences, Sunnybrook Research Institute, Toronto ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto ON, Canada.
authors.forename: Kristiana
authors.initials: K
authors.lastname: Xhima
authors.affiliation: Hurvitz Brain Sciences Program, Biological Sciences, Sunnybrook Research Institute, Toronto ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto ON, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Aubert
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000534:rehabilitation*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005106:Exploratory Behavior / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D065852:Spatial Memory / Q000502:physiology; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins; D001973:Bromodeoxyuridine
keywords: Alzheimer’s disease; amyloid pathology; neurogenesis; physical exercise; spatial memory