Folate and vitamin E deficiency impair cognitive performance in mice subjected to oxidative stress: differential impact on normal mice and mice lacking apolipoprotein E

Abstract

One factor contributing to the age-related decline in cognitive performance is increased oxidative stress, that can arise from environmental, nutritional, and/or genetic compromise. Folate deficiency has been linked to several age-related neurodegenerative conditions, including Alzheimer's disease (AD), at least in part by increasing oxidative stress. Folate deficiency also potentiates the impact of other known risk factors for AD. Adecrease in function of apolipoprotein E (ApoE), is associated with increased oxidative stress and is a risk factor for AD. We tested the combined impact of dietary deficiencies in folate and vitamin E, coupled with exposure to high dietary iron as a pro-oxidant, on cognitive performance in normal and ApoE-/- mice by monitoring the percent alternation in passive Y and T maze tests. Both normal and ApoE-/- mice displayed some cognitive impairment when deprived of folate and vitamin E and exposed to iron, but ApoE-/- mice were more severely affected. These findings highlight the potential combined impact of dietary deficiencies and genetic predisposition to neurodegeneration. They further leave open the possibility that one or more risk factors may remain latent, and neurodegeneration may ensue only following augmentation by one or more additional traumatic events or conditions.