Lifelong vitamin E intake retards age-associated decline of spatial learning ability in apoE-deficient mice

摘要

The potential for lifelong vitamin E supplementation to delay age-associated cognitive decline was tested in apoE-deficient and wild-type C57BL/6 mice. Beginning at eight weeks of age, the mice were maintained on a control diet or diets supplemented with dl-α-tocopheryl acetate yielding approximate daily intakes of either 20 or 200 mg/kg body weight. When 6 or 18 months of age, cognitive functioning of the mice was assessed using swim maze and discriminated avoidance testing procedures. For the mice maintained on control diets, the age-related declines in swim maze performance were relatively larger in apoE-deficient mice when compared with wild-type. On the other hand, age-associated declines in learning and working memory for discriminated avoidance were similar in the two genotypes. The 200-mg/kg dose of vitamin E prevented the accelerated decline in spatial learning apparent in 18-month-old apoE-deficient mice, but had no equivalent effect on performance declines attributable to normal aging in the wild-type mice. Vitamin E supplementation failed to prevent age-related impairments in learning and memory for discriminated avoidance observed in both the wild-type and apoE-deficient mice. The current findings are consistent with the hypothesis that apoE deficiency confers an accelerated, though probably selective, loss of brain function with age. This loss of function would appear to involve pathogenic oxidative mechanisms that can be prevented or offset by antioxidant supplementation.