title: Cognitive and physical activity differently modulate disease progression in the amyloid precursor protein (APP)-23 model of Alzheimer's disease.
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.
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin-Buch, Charité University Medicine, Berlin, Germany.
authors.forename: Susanne A
authors.initials: SA
authors.lastname: Wolf
authors.forename: Golo
authors.initials: G
authors.lastname: Kronenberg
authors.forename: Kathrin
authors.initials: K
authors.lastname: Lehmann
authors.forename: Aaron
authors.initials: A
authors.lastname: Blankenship
authors.forename: Rupert
authors.initials: R
authors.lastname: Overall
authors.forename: Matthias
authors.initials: M
authors.lastname: Staufenbiel
authors.forename: Gerd
authors.initials: G
authors.lastname: Kempermann
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000473:pathology* / Q000523:psychology*; D016564:Amyloid beta-Protein Precursor / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D002452:Cell Count; D002540:Cerebral Cortex / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D018450:Disease Progression; D004777:Environment; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D006624:Hippocampus / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology*; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D020933:Neurotrophin 3 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D020932:Nerve Growth Factor