Abstract

Early iron deficiency is associated with impaired (cognitive) development, the severity of which depends on the timing and duration of the under-supply of iron. To design effective treatment and prevention strategies for iron deficiency in humans, suited animal models are needed. In an earlier study (Antonides et al., 2015b) we separated 10 pairs of piglets from their mothers within a few days after birth and reared one sibling with artificial iron-deficient (ID) and the other with balanced control milk until weaning. ID piglets grew slower and showed poorer reference memory (RM) performance than their controls in a spatial holeboard task, even weeks after iron repletion. One putative intervening factor in that study was pre-weaning maternal deprivation. In an attempt to refine the piglet iron-deficiency model, we assessed whether piglets reared by sows, but withheld iron supplementation, can serve as animal model of iron deficiency. As sow milk is inherently ID, piglets normally receive a prophylactic iron injection. Ten pairs of piglets were housed with foster sows until weaning (4 weeks). One sibling per pair was randomly assigned to the control group (receiving iron dextran injections: 40 mg iron per kilogram body mass on days 3 and 10), the other to the ID group. From weaning, all pigs were fed a balanced commercial diet. Blood samples were taken in week 1, 3.5, 6, and 12. Pre-weaning blood iron values of ID piglets were lower than those of controls, but recovered to normal values after weaning. Hemoglobin of ID piglets did not reach anemic values. Hematocrit and hemoglobin of ID animals did not decrease, and serum iron even increased pre-weaning, suggesting that the piglets had access to an external source of iron, e.g., spilled feed or feces of the foster sows. Growth, and spatial memory assessed in the holeboard from 10 to 16 weeks of age, was unaffected in ID pigs. We conclude that sow-raised piglets are not a suitable model for iron-deficiency induced cognitive deficits in humans. Based on our previous and the present study, we conclude that growth and memory are only impaired in piglets that suffered from pre-weaning anemia.

Highlights

  • Iron deficiency is a form of malnutrition that is caused by a nutritional shortage of the micronutrient iron

  • We investigated whether piglets that stayed with the sow until weaning without receiving iron supplementation might serve as a suited, refined animal model for iron deficiency in humans

  • We compared blood iron values within ID animals between these sampling time points using one-sample t-statistics on the difference scores. These tests revealed that there was no difference in ID piglets’ Hct (t9 = 0.95; p = 0.37) and Hb (t9 = 0.99; p = 0.35) values between week 1 and 3.5, whereas their serum iron values were higher in week 3.5 than in week 1 (t9 = 3.29; p = 0.01)

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Summary

Introduction

Iron deficiency is a form of malnutrition that is caused by a nutritional shortage of the micronutrient iron. If iron shortage during early development is not restored quickly enough, neonates are at risk of developing iron deficiency, and eventually anemia. Early-life iron deficiency in humans is known to cause retarded growth and irreversible deficits in the development of motor and cognitive skills and memory functions (Beard, 2003; Lozoff and Georgieff, 2006). Rodent models have elucidated some important mechanisms involved in the development of iron deficiency, on both the (neuro)physiological and behavioral level. Results from both human and rodent studies suggest that earlylife iron deficiency causes irreversible deficits in brain structure and function (Yehuda and Youdim, 1989; Lozoff and Georgieff, 2006)

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