title: Behavior and monoamine deficits in prenatal and perinatal iron deficiency are not corrected by early postnatal moderate-iron or high-iron diets in rats.
abstract: Developmental iron deficiency anemia (IDA) causes brain and behavioral deficits in rodent models, which cannot be reversed when treated at periods equivalent to later infancy in humans. This study sought to determine whether earlier iron treatment can normalize deficits of IDA in rats and what iron dose is optimal. The offspring of dams with IDA during gestation were cross-fostered at postnatal d (P) 8 to dams receiving diets with 1 of 3 iron concentrations until weaning (P21): 0.003-0.01 g/kg [totally iron deficient (TID)]; 0.04 g/kg [formerly iron deficient (FID-40)]; or 0.4 g/kg (FID-400). Always iron-sufficient control dams (CN-40) received a 0.04-g/kg iron diet. At P21, TID pups received a 0.01 g iron/kg diet; all others received a 0.04 g iron/kg diet. Hematocrit and brain iron and monoamine concentrations were assessed at P21 and P100. Pup growth, development, activity, object recognition, hesitancy, and watermaze performance were evaluated. Regional brain iron was restored by iron treatment. Regional monoamine and metabolite concentrations were elevated in FID-40 rats and reduced in FID-400 and TID rats compared with CN-40 rats. FID-40 offspring had motor delays similar to TID during lactation and FID-400 rats had elevated thigmotaxis similar to TID rats at P25 and P100 in the spatial watermaze. In conclusion, iron treatment at P8 in rats did not normalize all monoamine or behavioral measures after early IDA. Moderate iron treatment improved adult behavior, but higher iron treatment caused brain and behavioral patterns similar to TID in the short and long term.
authors.affiliation: Department of Nutrition, Pennsylvania State University, University Park, PA, USA.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Unger
authors.forename: Amy R
authors.initials: AR
authors.lastname: Hurst
authors.forename: Michael K
authors.initials: MK
authors.lastname: Georgieff
authors.forename: Tim
authors.initials: T
authors.lastname: Schallert
authors.forename: Raghavendra
authors.initials: R
authors.lastname: Rao
authors.forename: James R
authors.initials: JR
authors.lastname: Connor
authors.forename: Niko
authors.initials: N
authors.lastname: Kaciroti
authors.forename: Betsy
authors.initials: B
authors.lastname: Lozoff
authors.forename: Barbara
authors.initials: B
authors.lastname: Felt
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000188:drug therapy*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D007501:Iron / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D008892:Milk / Q000737:chemistry; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015306:Biogenic Monoamines; D007501:Iron