Iron deficiency remains one of the foremost nutrient deficiencies in the world. Its effect on the developing brain and subsequent neurodevelopmental outcome is of particular importance. Our laboratory has characterized two groups of infants at increased risk of iron deficiency in the fetal and neonatal period; infants born to diabetic mothers (IDM) and intrauterine growth-retarded (IUGR) infants. Altered perinatal iron metabolism affects approximately 225,000 newborn infants per year in the United States. Both risk groups have altered neurodevelopment. We hypothesize that fetal iron deficiency contributes to their long-term neurological abnormalities. Our long-term objectives are to: 1) study the ontogeny of proteins involved in regulation of placental iron transport during pregnancies complicated by fetal iron deficiency; and 2) document the postnatal neurological sequelae of fetal iron deficiency. We hypothesize that: 1) placental transferring receptor (TfR) and HFE protein expression are regulated by fetal iron demand in IUGR pregnancies.; 2) fetal brain iron deficiency in IUGR pregnancies; 2) fetal brain iron deficiency in IUGR contributes to abnormalities of hypocampally based recognition memory processing by selectively reducing neuronal metabolism in the hippocampus. TfR and HFE protein expression and localization, iron responsive protein-1 and TfR mRNA expression, and TfR binding characteristics will be compared between 10 term iron-deficient IUGR placentas and 10 iron-sufficient controls. Ten placentas at 14, 18, 22, 24-28, 30-34 and >34 weeks gestation from normal pregnancies will be studied immunohistochemically to determine the ontogeny of TfR and HFE expression and contrasted to expression of these proteins in iron-deficient IUGR placentas. Recognition memory processing in 16 iron-deficient IUGR infants will be compared electrophysiologically at birth, 6 and 24 months and behaviorally at 6, 12 and 24 months to 16 controls. Perinatally iron-deficient rats (+/- perinatal stressors) will have their cerebral metabolism assessed longitudinally by 9.4 T magnetic resonance spectroscopy to identify hippocampal abnormalities due to iron deficiency. The metabolic results will be correlated with behavior and histochemical changes.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD029421-08
Application #
6476776
Study Section
Nutrition Study Section (NTN)
Program Officer
Grave, Gilman D
Project Start
1994-12-01
Project End
2004-11-30
Budget Start
2001-12-01
Budget End
2002-11-30
Support Year
8
Fiscal Year
2002
Total Cost
$306,817
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Pediatrics
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Barks, Amanda; Hall, Anne M; Tran, Phu V et al. (2018) Iron as a model nutrient for understanding the nutritional origins of neuropsychiatric disease. Pediatr Res :
Georgieff, Michael K; Ramel, Sara E; Cusick, Sarah E (2018) Nutritional influences on brain development. Acta Paediatr 107:1310-1321
Cusick, Sarah E; Georgieff, Michael K; Rao, Raghavendra (2018) Approaches for Reducing the Risk of Early-Life Iron Deficiency-Induced Brain Dysfunction in Children. Nutrients 10:
Condon, David E; Tran, Phu V; Lien, Yu-Chin et al. (2018) Defiant: (DMRs: easy, fast, identification and ANnoTation) identifies differentially Methylated regions from iron-deficient rat hippocampus. BMC Bioinformatics 19:31
Georgieff, Michael K; Tran, Phu V; Carlson, Erik S (2018) Atypical fetal development: Fetal alcohol syndrome, nutritional deprivation, teratogens, and risk for neurodevelopmental disorders and psychopathology. Dev Psychopathol 30:1063-1086
Wallin, Diana J; Zamora, Tara G; Alexander, Michelle et al. (2017) Neonatal mouse hippocampus: phlebotomy-induced anemia diminishes and treatment with erythropoietin partially rescues mammalian target of rapamycin signaling. Pediatr Res 82:501-508
Bastian, T W; Duck, K A; Michalopoulos, G C et al. (2017) Eltrombopag, a thrombopoietin mimetic, crosses the blood-brain barrier and impairs iron-dependent hippocampal neuron dendrite development. J Thromb Haemost 15:565-574
Cusick, Sarah E; Georgieff, Michael K (2016) The Role of Nutrition in Brain Development: The Golden Opportunity of the ""First 1000 Days"". J Pediatr 175:16-21
Zamora, Tara G; Guiang 3rd, Sixto F; Widness, John A et al. (2016) Iron is prioritized to red blood cells over the brain in phlebotomized anemic newborn lambs. Pediatr Res 79:922-8
Tran, Phu V; Kennedy, Bruce C; Pisansky, Marc T et al. (2016) Prenatal Choline Supplementation Diminishes Early-Life Iron Deficiency-Induced Reprogramming of Molecular Networks Associated with Behavioral Abnormalities in the Adult Rat Hippocampus. J Nutr 146:484-93

Showing the most recent 10 out of 59 publications