Exercise improves cognition and hippocampal plasticity in APOE ε4 mice

Abstract 

Background

Human studies on exercise, cognition, and apolipoprotein E (APOE) genotype show that ε4 carriers may benefit from regular physical activity.

Methods

We examined voluntary wheel-running, memory, and hippocampal plasticity in APOE ε3 and APOE ε4 transgenic mice at 10–12 months of age.

Results

Sedentary ε4 mice exhibited deficits in cognition on the radial-arm water maze (RAWM), a task dependent on the hippocampus. Six weeks of wheel-running in ε4 mice resulted in improvements on the RAWM to the level of ε3 mice. Hippocampal brain-derived neurotrophic factor (BDNF) levels were similar in ε3 and ε4 mice, and after exercise BDNF was similarly increased in both ε3 and ε4 mice. In sedentary ε4 mice, tyrosine kinase B (Trk B) receptors were reduced by 50%. Exercise restored Trk B in ε4 mice to the level of ε3 mice, and in ε4 mice, exercise dramatically increased synaptophysin, a marker of synaptic function.

Conclusions

Our results support the hypothesis that exercise can improve cognitive function, particularly in ε4 carriers.

Keywords: Exercise, APOE, Behavior, BDNF, Plasticity