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Chronic marginal iron intakes during early development in mice result in persistent changes in dopamine metabolism
C L Kwik-Uribe1, D Gietzen, J B German
1Department of Nutrition, University of California, Davis, CA 95616, USA.
Abstract:
Marginal iron (Fe) deficiency is prevalent in children worldwide, yet the behavioral and biochemical effects of chronic marginal Fe intakes during early development are not well characterized. Using a murine model, previous work in our laboratory demonstrated persistent behavioral disturbances as a consequence of marginal Fe intakes during early development. In the present study, Swiss-Webster mice fed a control Fe diet (75 microgram Fe/g diet, n = 13 litters) or marginal Fe diet (14 microgram Fe/g diet, n = 16 litters) during gestation and through postnatal day (PND) 75 were killed on PND 75 for assessment of tissue mineral concentrations, dopamine metabolism, myelin fatty acid composition, and c- and m-aconitase activities. In addition, these outcomes were assessed in a group of offspring (n = 13 litters) fed a marginal Fe diet during gestation and lactation and then fed a control diet from PND 21-75. Marginal Fe mice demonstrated significant differences in brain iron concentrations, dopamine metabolism and myelin fatty acid composition relative to control mice; however, no difference in c- or m-aconitase activity was demonstrated in the brain. The postnatal consumption of Fe-adequate diets among marginal Fe offspring did not fully reverse all of the observed biochemical disturbances. This study demonstrates that chronic marginal Fe intakes during early development can result in significant changes in brain biochemistry. The persistence of some of these biochemical changes after postnatal Fe supplementation suggests that they are an irreversible consequence of developmental Fe restriction.
Insights
Marginal iron deficiency in early development causes lasting brain biochemistry changes in mice. Even with later iron repletion, some effects persist, indicating irreversible developmental impacts.
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Marginal iron deficiency is common in children globally.
- Its long-term effects on early development are not fully understood.
- Previous studies showed persistent behavioral issues from marginal iron intake.
Purpose of the Study:
- To investigate the biochemical consequences of marginal iron deficiency during early development.
- To assess if later iron supplementation can reverse these effects.
Main Methods:
- Mice were fed control or marginal iron diets during gestation and early life.
- Brain tissue was analyzed for iron, dopamine, myelin fatty acids, and enzyme activity.
- One group received iron supplementation after weaning.
Main Results:
- Marginal iron intake altered brain iron concentration, dopamine metabolism, and myelin fatty acid composition.
- No changes in brain aconitase activity were observed.
- Postnatal iron supplementation did not fully reverse all biochemical alterations.
Conclusions:
- Chronic marginal iron deficiency during early development significantly alters brain biochemistry.
- Some biochemical changes persist even after iron repletion, suggesting irreversible developmental effects.