title: Ingestion of Mn and Pb by rats during and after pregnancy alters iron metabolism and behavior in offspring.
abstract: Manganese (Mn) and lead (Pb) exposures during developmental period can impair development by direct neurotoxicity or through interaction with iron metabolism. Therefore, we examined the effects of maternal ingestion of Mn or Pb in drinking water during gestation and lactation on iron metabolism as well as behavior in their offspring. Pregnant dams were given distilled water, 4.79mg/ml Mn, or 2.84mg/ml Pb in drinking water during gestation and lactation. Pups were studied at time of weaning for (59)Fe absorption from the gut, duodenal divalent metal transporter 1 (DMT1) expression, hematological parameters, and anxiety-related behavior using an Elevated Plus Maze (EPM) test. Metal-exposed pups had lower body weights and elevated blood and brain concentrations of the respective metal. Pb-exposed pups had lower hematocrits and higher blood Zn protoporphyrin levels. In contrast, Mn exposed pups had normal hematological parameters but significantly reduced Zn protoporphyrin. Pharmacokinetic studies using (59)Fe showed that intestinal absorption in metal-exposed pups was not different from controls, nor was it correlated with duodenal DMT1 expression. However, intravenously injected (59)Fe was cleared more slowly in Pb-exposed pups resulting in higher plasma levels. The overall tissue uptake of (59)Fe was lower in Mn-exposed and lower in the brain in Pb-exposed pups. The EPM test demonstrated that Mn-exposed, but not Pb-exposed, pups had lower anxiety-related behavior compared to controls. We conclude that gestational and lactational exposures to Mn or Pb differentially alter Fe metabolism and anxiety-related behavior. The data suggest that perturbation in Fe metabolism may contribute to the pathophysiologic consequences of Mn and Pb exposure during early development.
authors: Program in Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, United States. rmolina@hsph.harvard.edu
authors: Ramon M
authors: RM
authors: Molina
authors: Siripan
authors: S
authors: Phattanarudee
authors: Jonghan
authors: J
authors: Kim
authors: Khristy
authors: K
authors: Thompson
authors: Marianne
authors: M
authors: Wessling-Resnick
authors: Timothy J
authors: TJ
authors: Maher
authors: Joseph D
authors: JD
authors: Brain
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; D000375:Aging; D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000378:metabolism / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D027682:Cation Transport Proteins / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D007408:Intestinal Absorption / Q000187:drug effects; D007501:Iron / Q000097:blood / Q000378:metabolism*; D019189:Iron Metabolism Disorders / Q000139:chemically induced* / Q000378:metabolism; D007774:Lactation; D008297:Male; D017895:Manganese Compounds / Q000008:administration & dosage / Q000097:blood; D018811:Maternal Exposure; D009043:Motor Activity / Q000187:drug effects; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D002712:Chlorides; D007501:Iron; D017895:Manganese Compounds; D009942:Organometallic Compounds; D000099236:Solute Carrier Family 11, Member 2; C025340:manganese chloride; C008261:lead acetate