Early iron deficiency alters sensorimotor development and brain monoamines in rats.
Iron deficiency in human infancy reportedly leads to developmental delays and changes in neurobiology that may be irreversible. Using a rodent model, the present study examined whether dietary iron deficiency late in pregnancy and during lactation alters sensorimotor development and brain monoaminergic systems. Rats were assigned to 1 of 4 dietary treatments during gestation and lactation: 1) iron sufficient control; 2) prenatal iron deficiency beginning on gestational d 15 (G15); 3) postnatal iron deficiency beginning on postnatal d 4 (P4); 4) iron deficiency beginning on G15 followed by an iron sufficient diet on P4. Developmental milestones, open field behavior, brain iron and proteins, monoamines, and their transporters were evaluated between P6 and P21. Only G15 iron deficient rats had greater dopaminergic activity than controls as indicated by increased tyrosine hydroxylase levels, phosphorylated tyrosine hydroxylase levels, and cellular dopamine in prefrontal cortex and striatum at P15. These rats also showed delayed eye opening, ear development, and reduced locomotor activity. Iron repletion at P4 returned most measures to control levels by the time of weaning. Postnatal iron deficiency reduced striatal and ventral midbrain iron as well as cellular dopamine levels in prefrontal cortex and striatum at P21. Developmental delays in ear development and achievement in bar holding and surface righting also resulted from postnatal iron deficiency. These results indicate that iron deficiency begun at G15 affects early dopamine neurobiology, the development of specific developmental milestones, and behavior in preweaned rats.
Unger
Erica L
EL
Department of Nutrition Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
Paul
Tessy
T
Murray-Kolb
Laura E
LE
Felt
Barbara
B
Jones
Byron C
BC
Beard
John L
JL
D000375:Aging / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D007501:Iron / Q000378:metabolism; D000090463:Iron Deficiencies; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D015306:Biogenic Monoamines; D007501:Iron