Vitamin E protects against alcohol-induced cell loss and oxidative stress in the neonatal rat hippocampus.
Oxidative stress has been proposed as a possible mechanism underlying nervous system deficits associated with Fetal Alcohol Syndrome (FAS). Current research suggests that antioxidant therapy may afford some level of protection against the teratogenic effects of alcohol. This study examined the effectiveness of antioxidant treatment in alleviating biochemical, neuroanatomical, and behavioral effects of neonatal alcohol exposure. Neonatal rats were administered alcohol (5.25 g/kg) by intragastric intubation on postnatal days 7, 8, and 9. A subset of alcohol-exposed pups were co-administered a high dose of Vitamin E (2 g/kg, or 71.9 IU/g). Controls consisted of a non-treated group, a group given the administration procedure only, and a group given the administration procedure plus the Vitamin E dose. Ethanol-exposed animals showed impaired spatial navigation in the Morris water maze, a decreased number of hippocampal CA1 pyramidal cells, and higher protein carbonyl formation in the hippocampus than controls. Vitamin E treatment alleviated the increase in protein carbonyls and the reduction in CA1 pyramidal cells seen in the ethanol-exposed group. However, the treatment did not improve spatial learning in the ethanol-exposed animals. These results suggest that while oxidative stress-related neurodegeneration may be a contributing factor in FAS, the antioxidant protection against alcohol-induced oxidative stress and neuronal cell loss in the rat hippocampus does not appear to be sufficient to prevent the behavioral impairments associated with FAS. Our findings underscore the complexity of the pathogenesis of behavioral deficits in FAS and suggest that additional mechanisms beyond oxidative damage of hippocampal neurons also contribute to the disorder.