Ingestion of Mn and Pb by rats during and after pregnancy alters iron metabolism and behavior in offspring.
Ingestion of Mn and Pb by rats during and after pregnancy alters iron metabolism and behavior in offspring.
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DOI：
10.1016/j.neuro.2011.03.010
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发表时间：
2011-08
期刊：
影响因子：
3.4
通讯作者：
Brain JD
中科院分区：
文献类型：
--
作者：
Molina RM;Phattanarudee S;Kim J;Thompson K;Wessling-Resnick M;Maher TJ;Brain JD
发育期锰（Mn）和铅（Pb）暴露可通过直接神经毒性或通过与铁代谢的相互作用损害发育。因此，我们研究了母亲在妊娠期和哺乳期摄入饮用水中的锰或铅对铁代谢及其后代行为的影响。妊娠母鼠在妊娠期和哺乳期饮用蒸馏水、4.79 mg/ml Mn或2.84 mg/ml Pb。在断奶时，使用高架加迷宫（Elevated Plus Maze，EMAZ）试验研究幼鼠的肠道59 Fe吸收、十二指肠二价金属转运蛋白1（DMT 1）表达、血液学参数和焦虑相关行为。接触金属的幼崽体重较低，血液和大脑中相应金属的浓度升高。铅暴露的幼崽有较低的血细胞比容和较高的血锌原卟啉水平。与此相反，锰暴露的幼崽有正常的血液学参数，但显着减少锌原卟啉。使用59 Fe的药代动力学研究表明，金属暴露幼崽的肠道吸收与对照组没有差异，也与十二指肠DMT 1表达无关。然而，静脉注射的59 Fe在铅暴露的幼崽中清除得更慢，导致血浆水平更高。锰暴露组和铅暴露组幼鼠脑中59 Fe的总体组织摄取较低。该测试表明，锰暴露，但不铅暴露，幼崽有较低的焦虑相关行为相比，控制。我们得出结论，妊娠期和哺乳期暴露于锰或铅差异改变铁代谢和焦虑相关的行为。这些数据表明，扰动铁代谢可能有助于锰和铅暴露在早期发展的病理生理后果。
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, 4.79 mg/ml Mn, or 2.84 mg/ml Pb in drinking water during gestation and lactation. Pups were studied at time of weaning for 59Fe 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 59Fe showed that intestinal absorption in metal-exposed pups was not different from controls, nor was it correlated with duodenal DMT1 expression. However, intravenously injected 59Fe was cleared more slowly in Pb-exposed pups resulting in higher plasma levels. The overall tissue uptake of 59Fe 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.