This project deals with iron deficiency, the most common nutritional problem worldwide, and with exposure to alcohol, another problem common in the human population. Humans are most vulnerable and seriously impacted by these problems in pregnancy and postnatal development, with alcohol abuse being a major cause of mental retardation. Exposure to alcohol is a risk factor with many features in common with iron deficiency.
Five specific aims address the hypothesis that the less than optimum conditions of under-developed and over-developed white matter in immature brain, as conferred by a dietary iron deficiency and by dietary iron excess, respectively, are highly vulnerable, and at certain risk from exposure to alcohol. Our studies indicate the iron deficiency induced delay in white matter development is recouped later after dietary rehabilitation. Developing brain is especially vulnerable at the brain growth spurt/onset of myelination because it is entirely responsible for the biosynthetic capability to produce more than 95 % of the lipid it needs at this time. We propose there is a direct relationship between this absolute requirement for lipid accretion, and the delay, or over development, of white matter depending on iron status. Once alcohol is involved in conditions of dietary iron deficiency and excess, the injury may be irreversible. The magnitude of damage is to be assessed in aim i by examination of behavioral/cognitive function, and to ascertain if specific brain regions can be identified as critical targets.
Aim II examines marked for cellular injury, related to astrogliosis, oligodendroglial integrity and white matter development.
Aim III examines cellular markers related to the regulation of iron homeostasis and cellular stress.
Aim I V deals with lipid management where both passive and dynamic measures of lipid status can be related to age in development, and aim V addresses the function of the iron dependent complexes of the respiratory chain, which may be influenced directly by iron status, alcohol exposure, and by oxidative stress during its postnatal development. Our experimental model is the gastrostomy-reared rat pup which allows well defined and controlled experiments involving exclusively only the two variables, alcohol exposure and dietary iron status as components of the study.
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