Behavioral consequences of marginal iron deficiency during development in a murine model.

Abstract

Marginal iron deficiency is a common nutritional disorder in human populations world-wide; however, the neurobehavioral effects of chronic marginal iron (Fe) intakes during development are poorly characterized in animals. For this reason, we investigated whether mice reared on marginal Fe diets during pre- and postnatal development would experience neurobehavioral deficits. Swiss-Webster mice reared on either control (75 ppm Fe) or marginal iron (12.5 ppm) diets were assessed for changes in behavior on postnatal days 30, 40, and 50 using a neurobehavioral test battery. Because alterations in tissue mineral status can lead to an oxidative stress, markers of both protein (glutamine synthetase) and lipid oxidation (TBARS) were measured. Marginal iron animals exhibited a 20-55% reduction in grip strength. Although both marginal iron males and females demonstrated persistent lowering of body weights, statistical analysis using weight as the covariate demonstrated that the grip strength reductions were independent of body weight changes. This reduction in grip strength occurred in conjunction with a 25-45% lowering of brain iron in the marginal iron animals. Despite dramatic reductions in both brain and liver iron, hematocrits were unaffected by dietary iron reductions. Oxidative stress was indicated by an elevation in noniron-stimulated TBARS in the cerebellum of marginal iron animals. These data suggest that a chronic marginal Fe deficiency during critical periods of growth can result in functional changes in motor development even in the absence of iron deficiency anemia; furthermore, alterations in mineral status and oxidative stress may be mechanisms contributing to these observed changes.