title: Wheel-running in a transgenic mouse model of Alzheimer's disease: protection or symptom?
abstract: Several studies on both humans and animals reveal benefits of physical exercise on brain function and health. A previous study on TgCRND8 mice, a transgenic model of Alzheimer's disease, reported beneficial effects of premorbid onset of long-term access to a running wheel on spatial learning and plaque deposition. Our study investigated the effects of access to a running wheel after the onset of Abeta pathology on behavioural, endocrinological, and neuropathological parameters. From day 80 of age, the time when Abeta deposition becomes apparent, TgCRND8 and wildtype mice were kept with or without running wheel. Home cage behaviour was analysed and cognitive abilities regarding object recognition memory and spatial learning in the Barnes maze were assessed. Our results show that, in comparison to Wt mice, Tg mice were characterised by impaired object recognition memory and spatial learning, increased glucocorticoid levels, hyperactivity in the home cage and high levels of stereotypic behaviour. Access to a running wheel had no effects on cognitive or neuropathological parameters, but reduced the amount of stereotypic behaviour in transgenics significantly. Furthermore, wheel-running was inversely correlated with stereotypic behaviour, suggesting that wheel-running may have stereotypic qualities. In addition, wheel-running positively correlated with plaque burden. Thus, in a phase when plaques are already present in the brain, it may be symptomatic of brain pathology, rather than protective. Whether or not access to a running wheel has beneficial effects on Alzheimer-like pathology and symptoms may therefore strongly depend on the exact time when the wheel is provided during development of the disease.
authors.affiliation: Department of Behavioural Biology, University of Münster, Badestrasse 13, Münster, Germany. helene.s.richter@vetmed.uni-giessen.de
authors.forename: Helene
authors.initials: H
authors.lastname: Richter
authors.forename: Oliver
authors.initials: O
authors.lastname: Ambrée
authors.forename: Lars
authors.initials: L
authors.lastname: Lewejohann
authors.forename: Arne
authors.initials: A
authors.lastname: Herring
authors.forename: Kathy
authors.initials: K
authors.lastname: Keyvani
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.forename: Rupert
authors.initials: R
authors.lastname: Palme
authors.forename: Chadi
authors.initials: C
authors.lastname: Touma
authors.forename: Wolf-Rüdiger
authors.initials: WR
authors.lastname: Schäbitz
authors.forename: Norbert
authors.initials: N
authors.lastname: Sachser
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D006801:Humans; D008297:Male; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009483:Neuropsychological Tests; D010364:Pattern Recognition, Visual / Q000502:physiology; D058225:Plaque, Amyloid / Q000473:pathology; D012420:Running / Q000502:physiology*; D013239:Stereotyped Behavior / Q000502:physiology
chemical_list: D016564:Amyloid beta-Protein Precursor; D003345:Corticosterone