The principal long-term goal of this research is to determine the extent to which iron deficiency anemia (IDA)in early life leads to changes in monoamine biology with related changes in behavior. We will also determine when in development the effect becomes irreversible despite later iron therapy. It is abundantly clear that iron deficiency in early life impairs the biobehavioral development of millions of young children and infants. The previously funded project demonstrated that brain iron deficiency pro and post weaning results in dramatic changes in dopamine metabolism. We demonstrated decreases in dopamine (DA) uptake, DA transporter (DAT) density, and in DA (D1 and D2) receptor density. Iron repletion only restored some of these measures of neurotransmitter metabolism to normal. Certain behaviors, like """"""""exploration"""""""" or """"""""anxiety"""""""" were related to caudate and prefrontal cortex iron and dopamine variables. Recent pilot studies suggest that metabolism of all central nervous system monoamines (serotonin, norepinephrine, and dopamine) is sensitive to brain iron deficiency. We now hypothesize that brain iron deficiency results in alterations in all three monoamine systems.
Specific Aim 1 : To demonstrate the extent to which brain iron deficiency during preweaning results in irreversible changes in monoamine metabolism using both short and long term repletion research designs. The hypothesis is that early pre-weaning iron deficiency leads to significant changes in neuronal functioning that are irreversible with iron repletion.
Specific Aim 2 : To determine the extent to which brain iron deficiency during preweaning alters the emergence of motor and behavioral activities. We will determine the extent to which specific behaviors are related to the alterations in monoamine metabolism measured in Aim 1 through statistical models.
Specific Aim 3 : To determine the mechanism by which iron deficiency affects the metabolism of moneamine transporters and receptors. These cell culture studies will test the hypothesis that neuronal iron deficiency results in a decrease in the expression of monoamine transporters and potentially monoamine receptors through regulation of gone expression and protein trafficking. This expansion of study to other neurotransmitters will significantly contribute to our knowledge of the effects of iron deficiency on brain functioning in early life.
| Bianco, Laura E; Unger, Erica L; Earley, Christopher J et al. (2009) Iron deficiency alters the day-night variation in monoamine levels in mice. Chronobiol Int 26:447-63 |
| Unger, Erica L; Earley, Christopher J; Beard, John L (2009) Diurnal cycle influences peripheral and brain iron levels in mice. J Appl Physiol 106:187-93 |
| Connor, James R; Wang, Xin-Sheng; Allen, Richard P et al. (2009) Altered dopaminergic profile in the putamen and substantia nigra in restless leg syndrome. Brain 132:2403-12 |
| Unger, Erica L; Wiesinger, Jason A; Hao, Lei et al. (2008) Dopamine D2 receptor expression is altered by changes in cellular iron levels in PC12 cells and rat brain tissue. J Nutr 138:2487-94 |
| Bianco, Laura E; Wiesinger, Jason; Earley, Christopher J et al. (2008) Iron deficiency alters dopamine uptake and response to L-DOPA injection in Sprague-Dawley rats. J Neurochem 106:205-15 |
| Jones, L C; Earley, C J; Allen, R P et al. (2008) Of mice and men, periodic limb movements and iron: how the human genome informs the mouse genome. Genes Brain Behav 7:513-4 |
| Wiesinger, Jason A; Buwen, James P; Cifelli, Christopher J et al. (2007) Down-regulation of dopamine transporter by iron chelation in vitro is mediated by altered trafficking, not synthesis. J Neurochem 100:167-79 |
| Beard, John L; Unger, Erica L; Bianco, Laura E et al. (2007) Early postnatal iron repletion overcomes lasting effects of gestational iron deficiency in rats. J Nutr 137:1176-82 |
| Unger, Erica L; Beard, John L; Jones, Byron C (2007) Iron regulation in C57BLI6 and DBA/2 mice subjected to iron overload. Nutr Neurosci 10:89-95 |
| Jones, Byron C; Beard, John L; Gibson, Jennifer N et al. (2007) Systems genetic analysis of peripheral iron parameters in the mouse. Am J Physiol Regul Integr Comp Physiol 293:R116-24 |
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