Exercise training and antioxidant supplementation independently improve cognitive function in adult male and female GFAP-APOE mice

Purpose: The purpose of this study was to determine if antioxidant supplementation, moderate exercise, and the combination of both treatments could ameliorate cognitive performance in adult mice and whether the apolipoprotein E (APOE) genotype as well as sex could influence the functional outcomes of the treatments. Methods: For a period of 16 weeks, separate groups of male and female mice expressing either the human APOE3 or APOE4 isoforms were fed either a control diet (NIH-31) or the control diet supplemented with vitamins E and C (1.12 IU/g diet α-tocopheryl acetate and 1.65 mg/g ascorbic acid). The mice were further separated into a sedentary group or a group that followed a daily exercise regimen. After 8 weeks on the treatments, the mice were administered a battery of functional tests including tests to measure cognitive and affective function. Results: There was no effect of genotype or treatment on the learning performance in the Morris water maze. In the discriminated avoidance task, APOE4 mice performed better in learning the discrimination component of the task. Overall, exercise improved performance of APOE4 and APOE3 mice on various aspects of the active avoidance task. Antioxidant supplementation improved performance only in the APOE4 mice. On the test for anxiety, APOE4 mice spent more time in the open arms and supplementation with antioxidant reversed that effect. Conclusion: Exercise was the most effective treatment at improving cognitive function in both genotypes and sex, while antioxidants seemed to be effective only in the APOE4. In young adult mice only non-spatial learning and memory were improved. The combination of the two treatments did not yield further improvement in cognition, and there was no antagonistic action of the antioxidant supplementation on the beneficial effects of exercise.