Ingestion of Mn and Pb by rats during and after pregnancy alters iron metabolism and behavior in offspring

Molina, RM; Phattanarudee, S; Kim, J; Thompson, K; Wessling-Resnick, M; Maher, TJ; Brain, JD

HERO ID

786611

Reference Type

Journal Article

Year

2011

Language

English

PMID

21458486

HERO ID 786611
In Press No
Year 2011
Title Ingestion of Mn and Pb by rats during and after pregnancy alters iron metabolism and behavior in offspring
Authors Molina, RM; Phattanarudee, S; Kim, J; Thompson, K; Wessling-Resnick, M; Maher, TJ; Brain, JD
Journal NeuroToxicology
Volume 32
Issue 4
Page Numbers 413-422
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.
Doi 10.1016/j.neuro.2011.03.010
Pmid 21458486
Wosid MEDLINE:21458486
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English
Keyword neurotoxicity; biomarker; heavy metals; iron metabolism; anxiety; metal interaction