Vitamin E protects against PUFA‐induced behavioral and motor deficits (596.8)

Abstract

Vitamin E is a major lipid soluble antioxidant that scavenges free radicals generated by lipid peroxidation of polyunsaturated fatty acids (PUFAs). Deficiency of this essential nutrient manifests primarily as neurological degeneration. Mutations in the alpha‐tocopherol transfer protein (TTP), the key regulator of whole‐body vitamin E levels, present with extremely low vitamin E levels, oxidative stress, and progressive cerebellar ataxia. Western diets trend towards increased and imbalanced consumption of n‐6 PUFA, thought to be associated with cardiovascular disease, asthma and Multiple Sclerosis and other diseases. We aimed to understand the relationship between PUFA intake, vitamin E status, and neurological function. To this end, we utilized the Ttpa‐null mouse model that faithfully recapitulates vitamin E deficiency in humans. We aimed to exacerbate oxidative stress and neurological deficits by maintaining the mice on a diet high in n‐6 PUFA (corn oil). The wild type mice, which exhibited ample vitamin E levels showed no signs of ataxia, regardless of the PUFA intakes. Vitamin E deficient Ttpa‐null mice fed high‐PUFA diet displayed the initial symptoms of ataxia at ~ 6 months of age, significantly earlier than animals that that were not supplemented with an n‐6 diet. Behavioral tests that assess anxiety and reactivity indicated a correlation between vitamin E status and the levels of PUFA in the diet. Most notable was a spontaneous jumping phenotype displayed when animals were removed from their cage. Future biochemical and histological assessments will explain the relationship between anxiety, oxidative stress and anatomic injuries. These findings indicate that adequate vitamin E status is required to combat deleterious neurological effects of PUFA‐rich diets.Grant Funding Source: Supported by T32DK07319 and RO1DK067494