The goal of this project is to evaluate the structural and behavioral effects of region and temporally specific iron deficiency (ID) on the developing hippocampus in a mouse conditional knockout model. The hippocampus is widely recognized as having paramount importance in several cognitive functions, including learning and memory. Unfortunately, the hippocampus is more susceptible than other brain areas during the perinatal period to many insults such as ID (Erickson et al, 1997). ID is the most prevalent micronutrient deficiency in the world, and affects some 250,000 neonates each year in the USA alone. Cognitive deficits resulting from perinatal ID persist into adulthood (Lozoff et al, 2000). Animal studies utilizing dietary restriction (which is a different etiology of ID than is seen in humans in the US) of iron have shown structural, biochemical, and cognitive impairments, but fail to clarify whether the effect on the hippocampus is indeed due to ID in the cells comprising the hippocampus, or due to other pathophysiological states that occur in conjunction with dietary ID (anemia, hypoxia). We are using a conditional KO model of an iron transporter (DMT1), and will examine its effects on structural and behavioral phenotypes related to learning & memory. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS047876-02
Application #
7101906
Study Section
Special Emphasis Panel (ZRG1-F06 (20))
Program Officer
Tagle, Danilo A
Project Start
2005-07-08
Project End
2007-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
2
Fiscal Year
2006
Total Cost
$27,674
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Neurosciences
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Fretham, Stephanie J B; Carlson, Erik S; Georgieff, Michael K (2013) Neuronal-specific iron deficiency dysregulates mammalian target of rapamycin signaling during hippocampal development in nonanemic genetic mouse models. J Nutr 143:260-6
Fretham, S J B; Carlson, E S; Wobken, J et al. (2012) Temporal manipulation of transferrin-receptor-1-dependent iron uptake identifies a sensitive period in mouse hippocampal neurodevelopment. Hippocampus 22:1691-702
Fretham, Stephanie J B; Carlson, Erik S; Georgieff, Michael K (2011) The role of iron in learning and memory. Adv Nutr 2:112-21
Carlson, Erik S; Fretham, Stephanie J B; Unger, Erica et al. (2010) Hippocampus specific iron deficiency alters competition and cooperation between developing memory systems. J Neurodev Disord 2:133-43
Carlson, Erik S; Tkac, Ivan; Magid, Rhamy et al. (2009) Iron is essential for neuron development and memory function in mouse hippocampus. J Nutr 139:672-9
Tran, Phu V; Fretham, Stephanie J B; Carlson, Erik S et al. (2009) Long-term reduction of hippocampal brain-derived neurotrophic factor activity after fetal-neonatal iron deficiency in adult rats. Pediatr Res 65:493-8
Carlson, Erik S; Magid, Rhamy; Petryk, Anna et al. (2008) Iron deficiency alters expression of genes implicated in Alzheimer disease pathogenesis. Brain Res 1237:75-83
Carlson, Erik S; Stead, John D H; Neal, Charles R et al. (2007) Perinatal iron deficiency results in altered developmental expression of genes mediating energy metabolism and neuronal morphogenesis in hippocampus. Hippocampus 17:679-91