Cognitive and Physical Activity Differently Modulate Disease Progression in the Amyloid Precursor Protein (APP)-23 Model of Alzheimer’s Disease

• Published in: Biological psychiatry (1969) 2006-12, Vol.60 (12), p.1314-1323
• Main Authors: Wolf, Susanne A., Kronenberg, Golo, Lehmann, Kathrin, Blankenship, Aaron, Overall, Rupert, Staufenbiel, Matthias, Kempermann, Gerd
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Adult neurogenesis; Alzheimer Disease - chemically induced; Alzheimer Disease - pathology; Alzheimer Disease - psychology; Amyloid beta-Protein Precursor - toxicity; Animals; Biological and medical sciences; Brain - pathology; Brain-Derived Neurotrophic Factor - biosynthesis; Brain-Derived Neurotrophic Factor - genetics; Cell Count; Cerebral Cortex - metabolism; Cognition - physiology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; enriched environment; Environment; Female; Fibroblast Growth Factor 2 - biosynthesis; Hippocampus - metabolism; Insulin-Like Growth Factor I - biosynthesis; Maze Learning - physiology; Medical sciences; Mice; Mice, Transgenic; Motor Activity - physiology; mouse; Nerve Growth Factor - biosynthesis; Nerve Growth Factor - genetics; Neurology; neurotrophin; Neurotrophin 3 - biosynthesis; Neurotrophin 3 - genetics; Organic mental disorders. Neuropsychology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; stem cell; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - genetics; water maze
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2006.04.004

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). Amyloid precursor protein (APP)-23 mice were housed under standard or enriched conditions or in cages equipped with a running wheel. We assessed β-amyloid plaque load, adult hippocampal neurogenesis, spatial learning, and mRNA levels of trophic factors in the brain. Despite stable β-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. 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.