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Thompson, Khristy

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Thompson

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Khristy

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Thompson, Khristy
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    Ingestion of Mn and Pb by rats during and after pregnancy alters iron metabolism and behavior in offspring
    (Elsevier BV, 2011) Molina, Ramon; Phattanarudee, Siripan; Kim, Jonghan; Thompson, Khristy; Wessling-resnick, Marianne; Maher, Timothy Richard; Brain, Joseph
    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.
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    Iron-Responsive Olfactory Uptake of Manganese Improves Motor Function Deficits Associated with Iron Deficiency
    (Public Library of Science, 2012) Kim, Jonghan; Li, Yuan; Buckett, Peter; Böhlke, Mark; Thompson, Khristy; Takahashi, Masaya; Maher, Timothy J.; Wessling-resnick, Marianne
    Iron-responsive manganese uptake is increased in iron-deficient rats, suggesting that toxicity related to manganese exposure could be modified by iron status. To explore possible interactions, the distribution of intranasally-instilled manganese in control and iron-deficient rat brain was characterized by quantitative image analysis using T1-weighted magnetic resonance imaging (MRI). Manganese accumulation in the brain of iron-deficient rats was doubled after intranasal administration of \(MnCl_2\) for 1- or 3-week. Enhanced manganese level was observed in specific brain regions of iron-deficient rats, including the striatum, hippocampus, and prefrontal cortex. Iron-deficient rats spent reduced time on a standard accelerating rotarod bar before falling and with lower peak speed compared to controls; unexpectedly, these measures of motor function significantly improved in iron-deficient rats intranasally-instilled with \(MnCl_2\). Although tissue dopamine concentrations were similar in the striatum, dopamine transporter (DAT) and dopamine receptor \(D_1\) (D1R) levels were reduced and dopamine receptor \(D_2\) (D2R) levels were increased in manganese-instilled rats, suggesting that manganese-induced changes in post-synaptic dopaminergic signaling contribute to the compensatory effect. Enhanced olfactory manganese uptake during iron deficiency appears to be a programmed "rescue response" with beneficial influence onmotor impairment due to low iron status.