Dietary iron and the integrity of the developing rat brain: a study with the artificially-reared rat pup.
Inadequate iron nutrition is thought to affect many aspects of brain development. Iron is a component of enzyme systems in DNA synthesis, the respiratory chain, neurotransmitter and lipid metabolism. The iron content of the striatum increases post-natally, with neuronal differentiation, myelin lipid and receptor formation: Seventy percent of the iron in the brain is associated with myelin. In an attempt to dissociate the global effects of under-and/or malnutrition and to produce exclusively an iron deficiency, we have used the gastrostomy-reared rat pup fed milk substitutes which vary only in their iron content. To ensure the pups did not have adequate iron reserves at birth, dams were fed a meal diet of low iron content (3 ppm) throughout gestation. The pups were then artificially reared on milk with (43 ppm), and without added iron (2.5 ppm) from 6 up to 21 days after birth. At 21 days of age, body weights of iron deficient pups were about 90% those of control animals. At 21 days of age, the pups were weaned, then fed standard laboratory rat chow. Brain was examined at 42 days of age (for young adults) and up to 6 months of age (180 days as mature adults). Morphometric analysis of sagittal sections of the cerebellum at 21 and 63 days of age revealed a deficit in white matter formation in pups fed low-iron at 21 days of age when compared to controls. This deficit was partially recouped by age 63 days. By contrast, animals fed milk supplemented with iron showed greater definition in white matter formation than controls at 21 days of age; indicative of precocious maturation of the white matter tracts. Our findings indicate that iron deficiency, without under/mal-nutrition and other variables, does not result in extensive growth deficits in body and brain weight. However, the iron status profoundly influences the development of myelination in that the process is delayed in iron deficiency.