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Cognitive and physical activity differently modulate disease progression in the amyloid precursor protein (APP)-23 model of Alzheimer's disease

Item Type:Article
Title:Cognitive and physical activity differently modulate disease progression in the amyloid precursor protein (APP)-23 model of Alzheimer's disease
Creators Name:Wolf, S.A. and Kronenberg, G. and Lehmann, K. and Blankenship, A. and Overall, R. and Staufenbiel, M. and Kempermann, G.
Abstract:BACKGROUND: In aging mice, activity maintains hippocampal plasticity and adult hippocampal neurogenesis at a level corresponding to a younger age. Here we studied whether physical exercise and environmental enrichment would also affect brain plasticity in a mouse model of Alzheimer's disease (AD). METHODS: Amyloid precursor protein (APP)-23 mice were housed under standard or enriched conditions or in cages equipped with a running wheel. We assessed beta-amyloid plaque load, adult hippocampal neurogenesis, spatial learning, and mRNA levels of trophic factors in the brain. RESULTS: Despite stable beta-amyloid plaque load, enriched-living mice showed improved water maze performance, an up-regulation of hippocampal neurotrophin (NT-3) and brain-derived neurotrophic factor (BDNF) and increased hippocampal neurogenesis. In contrast, despite increased bodily fitness, wheel-running APP23 mice showed no change in spatial learning and no change in adult hippocampal neurogenesis but a down-regulation of hippocampal and cortical growth factors. CONCLUSIONS: We conclude that structural and molecular prerequisites for activity-dependent plasticity are preserved in mutant mice with an AD-like pathology. Our study might help explain benefits of activity for the aging brain but also demonstrates differences between physical and more cognitive activity. It also suggests a possible cellular correlate for the dissociation between structural and functional pathology often found in AD.
Keywords:Adult Neurogenesis, Stem Cell, Neurotrophin, Water Maze, Enriched Environment, Animals, Mice
Source:Biological Psychiatry
ISSN:0006-3223
Publisher:Elsevier (U.S.A.)
Volume:60
Number:12
Page Range:1314-1323
Date:15 December 2006
Official Publication:https://doi.org/10.1016/j.biopsych.2006.04.004
PubMed:View item in PubMed

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