Iron acquisition and expression of iron regulatory proteins in the developing brain: manipulation by ethanol...

The World Health Organization considers iron deficiency the number one nutritional disorder in the world. In this review, the normal pattern for iron accumulation and expression of iron regulatory proteins (transferrin and its receptor, and ferritin) in brain during development are examined biochemically and at the cellular and molecular levels. Iron and the iron-regulatory proteins are at their highest postnatal concentration in the brain at birth, decline over the preweaning period and then increase to adult levels. Evidence is presented that in utero exposure to alcohol, iron-deficient diets, and dysfunctional oligodendrocytes can influence the normal pattern for iron accumulation in the brain which sets off a cascade of events that results in loss of regulatory control of iron. Because iron is an essential cofactor in neurotransmitter synthesis and myelination altering iron availability during vulnerable periods of development may have a permanent influence both on iron homeostasis in the brain and motor and cognitive function. At the cellular level, iron-positive cells in the subventricular zone and myelinogenic foci are present as early as postnatal day 3. Disruption of oligodendrocyte maturation is associated with altered expression and cellular accumulation of iron, transferrin and the transferrin receptor in brain. These data indicate that iron delivered via transferrin and its receptor is intrinsically involved in oligodendrocyte maturation and thus plays a critical role in the onset of myelination. In the adult, oligodendrocytes are the predominant iron-regulatory cell in the brain by virtue of their high content of iron, transferrin and ferritin. From these studies we conclude oligodendrocytes may be responsible for iron regulation in the brain at the cellular level and that brain iron regulatory mechanisms are vulnerable to manipulation during postnatal development.