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Exercise improves cognition and hippocampal plasticity in APOE ?4 mice

June 26th, 2009 by admin

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Abstract: Background: Human studies on exercise, cognition, and apolipoprotein E (APOE) genotype show that ?4 carriers may benefit from regular physical activity.Methods: We examined voluntary wheel-running, memory, and hippocampal plasticity in APOE ?3 and APOE ?4 transgenic mice at 10–12 months of age.Results: Sedentary ?4 mice exhibited deficits in cognition on the radial-arm water maze (RAWM), a task dependent on the hippocampus. Six weeks of wheel-running in ?4 mice resulted in improvements on the RAWM to the level of ?3 mice. Hippocampal brain-derived neurotrophic factor (BDNF) levels were similar in ?3 and ?4 mice, and after exercise BDNF was similarly increased in both ?3 and ?4 mice. In sedentary ?4 mice, tyrosine kinase B (Trk B) receptors were reduced by 50%. Exercise restored Trk B in ?4 mice to the level of ?3 mice, and in ?4 mice, exercise dramatically increased synaptophysin, a marker of synaptic function.Conclusions: Our results support the hypothesis that exercise can improve cognitive function, particularly in ?4 carriers.

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