EFFECTS OF APOE GENOTYPE, ANTIOXIDANTS AND EXERCISE ON MOTOR AND COGNITIVE FUNCTION

Purpose: The ɛ4 allele of apolipoprotein E (ApoE) has been associated with increased risk for development of late-onset Alzheimer's disease (AD). To prevent appearance of brain dysfunction, a healthy lifestyle, such as exercising and eating antioxidants, is often recommended. Physical activity has been shown to have an allele-specific beneficial effect on cognition in humans and rodents. Antioxidant therapy is often suggested to improve brain function, as increased oxidative stress has been correlated with brain dysfunction, especially in ɛ4 carriers. Health conscious individuals are likely to combine exercise with antioxidant intake to increase protection, however recent studies have indicated a negative interaction of these two factors. In some cases, antioxidant intake abolished the beneficial effects of exercise. Our study aimed at determining the nature of the interaction between exercise and antioxidants on functional outcomes in a model of increased AD risk. Methods: Young male and female mice, expressing the human ApoE3 or E4, were placed under one of the treatment: Sedentary/control diet (SedCon), Sedentary /antioxidant-rich diet (Vitamins E and C; SedEC), Exercise/control diet (EXCon), Exercise/ antioxidant-rich diet (EXEC), for 8 weeks prior to behavioral testing. Behavior testing includes running co-ordination (rotorod), spatial learning and memory (Morris Water Maze)and discriminative avoidance and cognitive flexibility (T maze). Results: In a coordination test, the E3 mice performed better than the E4 mice, and a significant improvement was observed with the ExEC treatment in males E3 and females E4. Better spatial learning was detected with EXEC in E3 females but not in E4. In males EX impaired learning index in E3 males. In active avoidance acquisition session, learning performance was improved with EX and EXEC treatment in E3 male, and with EXCon treatment in female E4, whereas cognitive flexibility was improved in both male and female in E3 by all the treatments but not in E4. Conclusions: These results in young mice provide an indication that genotype and sex are critical determinants in the functional outcomes of the treatment.