Hippocampal gene expression patterns underlying the enhancement of memory by running in aged mice.
Physical activity preserves cognition in the aging brain, but the mechanisms remain obscure. In order to identify candidate genes and pathways responsible for the preservation of cognitive function by exercise, we trained mice that had been exposed to lifelong running or sedentary lifestyle for 16 months in the hippocampus-dependent water maze. After water maze training, we analyzed the expression of 24,000 genes in the hippocampus using Illumina bead microarray. Runners show greater activation of genes associated with synaptic plasticity and mitochondrial function, and also exhibit significant downregulation of genes associated with oxidative stress and lipid metabolism. Running also modified the effects of learning on the expression of genes involved in cell excitability, energy metabolism, and insulin, MAP kinase and Wnt signaling. These results suggest that the enhancement of cognitive function by lifelong exercise is associated with an altered transcriptional profile following learning.
Stranahan
Alexis M
AM
Cellular and Molecular Neuroscience Section, Laboratory of Neurosciences, National Institute on Aging, Biomedical Research Center, 251 Bayview Boulevard, Baltimore, MD 21224-6825, United States. astrana1@jhu.edu
Lee
Kim
K
Becker
Kevin G
KG
Zhang
Yonqing
Y
Maudsley
Stuart
S
Martin
Bronwen
B
Cutler
Roy G
RG
Mattson
Mark P
MP
D000222:Adaptation, Physiological; D000375:Aging / Q000502:physiology*; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology; D005082:Physical Exertion / Q000502:physiology*; D012420:Running / Q000502:physiology; D013037:Spatial Behavior / Q000502:physiology
D009419:Nerve Tissue Proteins