Journal
BIOLOGICAL PSYCHIATRY
Volume 60, Issue 12, Pages 1314-1323Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2006.04.004
Keywords
adult neurogenesis; stem cell; neurotrophin; water maze; enriched environment; mouse
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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-amyloidplaque 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.
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