Iron deficiency is the most commonly reported nutritional deficiency in the world and has been linked to cognitive impairments in children. Our aim was to assess the impact of iron deficiency on cognition using neonatal piglets as a model for human infants, as neurodevelopment in piglets resembles that of humans. Piglets were fed one of three diets with varying concentrations of iron (Fe): adequate (6.3mg Fe/kg body weight [BW]), mildly deficient (1.5mg Fe/kg BW), or severely deficient (0.63 mg Fe/kg BW). Piglets were placed on the diet at two days of age for four weeks. On days 7, 14,21, and 28 hemoglobin (P = 0.0360) levels were reduced in piglets fed deficient diets. Skin pigmentation, as measured by a colorimeter in L*a*b* color space, showed reduced magenta color in the iron deficient piglets (P < 0.0001), correlating with hematocrit levels (R2 = 0.76). The effect of iron deficiency on cognition was assessed using a hippocampal-dependent spatial T-maze task. Severely deficient piglets were unable to acquire the task (P = 0.3937), while mildly deficient piglets had lower performance when the reward location was reversed than those on the adequate diet (P = 0.0321). This behavioral deficit was mirrored by a decrease in iron concentration in the hippocampus, but not the prefrontal cortex. Gene expression of several neurotrophic factors and proinflammatory cytokines, as well as whole-brain and hippocampal volume, were not affected.
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Iron deficiency affects spatial learning in neonatal piglets