Infants are at high risk for iron deficiency and iron-deficiency anemia. This review summarizes evidence of long-term effects of iron deficiency in infancy. Follow-up studies from preschool age to adolescence report poorer cognitive, motor, and social-emotional function, as well as persisting neurophysiologic differences. Research in animal models points to mechanisms for such long-lasting effects. Potential mechanisms relate to effects of iron deficiency during brain development on neurometabolism, myelination, and neurotransmitter function.

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Long-Lasting Neural and Behavioral Effects of Iron Deficiency in Infancy

The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-based advice to anyone with an interest in the role of nutrition in health. Specifically, the BOND program provides state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutrients in body tissues at the individual and population level. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, iron, zinc, folate, vitamin A, and vitamin B-12. This review represents the second in the series of reviews and covers all relevant aspects of folate biology and biomarkers. The article is organized to provide the reader with a full appreciation of folate's history as a public health issue, its biology, and an overview of available biomarkers (serum folate, RBC folate, and plasma homocysteine concentrations) and their interpretation across a range of clinical and population-based uses. The article also includes a list of priority research needs for advancing the area of folate biomarkers related to nutritional health status and development.

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Biomarkers of Nutrition for Development (BOND)-Iron Review.

Iron Deficiency and Brain Development

The environment and susceptibility to schizophrenia.

Iron is an essential trophic factor that is required for oxygen consumption and ATP production. Thus it plays a key role in vital cell functions. Although the brain has a relatively high rate of oxygen consumption compared to other organs, oligodendrocytes are the principal cells in the CNS that stain for iron under normal conditions. The importance of iron in myelin production has been demonstrated by studies showing that decreased availability of iron in the diet is associated with hypomyelination. The timing of iron delivery to oligodendrocytes during development is also important because hypomyelination and the associated neurological sequelae persist long after the systemic iron deficiency has been corrected. Therefore, identifying the molecular roles of iron in oligodendrocyte development and myelin production, and the mechanisms and timing of iron acquisitions are important prerequisites to developing effective therapies for dysmyelinating disorders. It is the purpose of this review to give a comprehensive overview of the existing literature on role of iron in oligodendrocytes and the mechanisms of iron acquisition and intracellular handling.

Oligodendrocytes and myelination: the role of iron.

Several observations suggest that iron is an essential factor in myelination and oligodendrocyte biology. However, the specific role of iron in these processes remains to be elucidated. This role could be as an essential cofactor in metabolic processes or as a transcriptional or translational regulator. In this study, we used animals models each with a unique defect in iron availability, storage, or transfer to test the hypothesis that disruptions in these mechanisms affect myelinogenesis and myelin composition. Disruption of iron availability either by limiting dietary iron or by altering iron storage capacity resulted in a decrease in myelin proteins and lipids but not the iron content of myelin. Among the integral myelin proteins, proteolipid protein was most consistently affected, suggesting that limiting iron to oligodendrocytes results not only in hypomyelination but also in a decrease in myelin compaction. Mice deficient in transferrin must receive transferrin injections beginning at birth to remain viable, and these mice had increases in all of the myelin components and in the iron content of the myelin. This finding indicates that the loss of endogenous iron mobility in oligodendrocytes could be overcome by application of exogenous transferrin. Overall, the results of this study demonstrate how myelin composition can be affected by loss of iron homeostasis and reveal specific chronic changes in myelin composition that may affect behavior and attempts to rescue myelin deficits.

G. Butkus

Papers

Effect of manipulation of iron storage, transport, or availability on myelin composition and brain iron content in three different animal models.