65 and 66

Overall, the APOE4 mice spent more time in the open arms than their APOE3 counterpart, results that are in contradiction with previous studies. 65 Furthermore, supplementation with vitamins influenced in a genotype-dependent manner the behavior of the mice on this task. In the APOE4 mice, the supplementation with antioxidants increased anxiety. This was in definite contrast with several studies relating that vitamin E depletion increases anxiety. 67 Furthermore, other studies have demonstrated a decrease in anxiety in rats supplemented with vitamins E and C. 68 In our active avoidance paradigm, the results differed depending on whether we analyzed the discriminative component or the avoidance component of the task. In the discriminative component, Enzalutamide in vivo which is the component of active avoidance that the mice learned first, there was a definite improvement in performance following exercise and antioxidant treatment in the APOE3 mice. The lack of significant improvement in the APOE4 mice could be due to a maximum plateau of performance due to the set criterion. The criterion was set as the number of trials to reach four out of five correct turns, therefore four trials would be the minimum number of trials than a mouse

could take. On average the SedCon APOE4 mice took between six and eight trials, thereby making it difficult to detect a significant effect of Treatment. The effects of Treatment were mostly due to exercise Treatment as the performance of the APOE3 mice remained largely Autophagy inhibitors unaffected by supplementation with antioxidants. In the avoidance component of the task, exercise training improved performance of the APOE mice, irrespective of genotype

in the acquisition phase. Interestingly, supplementation with antioxidants was only effective in the APOE4 mice. This is most likely due to the transporter protein being dysfunctional 69 and APOE4 mice having lower vitamin E levels, 70 therefore more responsive to antioxidant supplementation. Physical activity has been shown to reduce AD risk, 41, 42 and 43 to improve cognitive function and to have a positive impact on functional plasticity. 44 Interestingly, APOE4 allele carriers Liothyronine Sodium with a sedentary life style have been shown to be more vulnerable to excessive amyloid deposition in brain. 45 and 71 Physical activity levels have been strongly positively associated with cognitive function in individuals carrying APOE4 72 and 73 supported by transgenic mouse model carrying human APOE4. 33 These studies focused on individuals or mice in which cognitive dysfunction was present, while our study demonstrated that improvement can also be attained without apparent cognitive dysfunction and did not seem to be dependent upon the APOE genotype. Studies on combination of antioxidant and exercise have led to conflicting results.