Maternal stress modulates the effects of developmental lead exposure.
Maternal stress modulates the effects of developmental lead exposure.
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DOI：
10.1289/ehp.6481
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发表时间：
2004-05
影响因子：
10.4
通讯作者：
Bauter MR
中科院分区：
文献类型：
--
作者：
Cory-Slechta DA;Virgolini MB;Thiruchelvam M;Weston DD;Bauter MR
在美国，社会经济地位低的儿童与其他儿童相比，铅暴露水平更高。社会经济地位低本身是多种疾病和机能障碍的已知风险因素，这些影响归因于慢性应激以及相关的糖皮质激素升高。慢性升高的糖皮质激素和铅会引发类似的行为变化，并且两者都能作用于大脑的中脑边缘系统。在这项研究中，我们检验了这样一个假设：这些同时存在的风险因素，即铅和环境应激，会相互作用并调节彼此的影响。利用啮齿动物模型，我们重点研究了母体应激（束缚）和母体铅暴露（饮用水中含150ppm铅）对后代皮质酮水平的具体影响，以及对神经递质变化和一种对铅敏感的行为基线（固定间隔程序控制的行为表现）的影响。我们观察到铅和应激的相互作用因结果测量指标和性别而异。此外，增强效应（铅加应激的效应，但单独的铅或应激都未显示出这种变化）在雌性中更常见。重要的是，单独的铅（在雄性中）以及铅加应激（在雌性中）会使后代的皮质酮水平永久性升高；即使母鼠短期接触铅也会导致这种效应。这种升高可能提示一种潜在的新机制，通过该机制铅暴露可能直接或间接增加对疾病和机能障碍的易感性并导致认知缺陷。此外，铅和应激的相互作用效应，特别是铅加应激的增强效应，引发了关于当前风险评估策略是否充分考虑到并发风险因素可能导致的毒性调节潜力的问题。
Lead exposure is higher among children with low socioeconomic status (SES) compared with other children in the United States. Low SES itself is a known risk factor for various diseases and dysfunctions, effects that have been ascribed to chronic stress and associated elevation of glucocorticoids. Chronically elevated glucocorticoids and Pb provoke similar behavioral changes, and both can act on mesocorticolimbic systems of the brain. In this study we examined the hypothesis that these co-occurring risk factors, Pb and environmental stress, would interact and modulate each others' effects. Using a rodent model, we focused on the specific contributions of maternal stress (restraint) and maternal Pb exposure (150 ppm in drinking water) on corticosterone levels of offspring, as well as on neurotransmitter changes and a behavioral baseline (fixed-interval schedule-controlled performance) with known sensitivities to Pb. We observed interactions of Pb and stress that differed in relation to outcome measure and sex. In addition, potentiated effects (effects of Pb plus stress but showing no changes produced by either alone) were observed more frequently in females. Importantly, Pb alone (in males) and Pb plus stress (in females) permanently elevated corticosterone levels in offspring; even short-term Pb exposure to dams could cause this effect. Such increases could suggest a potential new mechanism by which Pb exposure could directly or indirectly enhance susceptibility to diseases and dysfunctions and induce cognitive deficits. Moreover, the interactive effects of Pb and stress, and particularly the potentiated effects of Pb plus stress, raise questions about whether current risk assessment strategies sufficiently consider the potential for modulation of toxicity that can accrue from intercurrent risk factors.
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影响因子：
3.3
作者：
BROSSCHOT, JF;BENSCHOP, RJ;BALLIEUX, RE
通讯作者：
BALLIEUX, RE
影响因子：
2.9
作者：
Chou-Green, JM;Holscher, TD;Akana, SF
通讯作者：
Akana, SF
影响因子：
1.5
作者：
ARDILA, A;ROSSELLI, M
通讯作者：
ROSSELLI, M
影响因子：
158.5
作者：
Canfield, RL;Henderson, CR;Lanphear, BP
通讯作者：
Lanphear, BP
影响因子：
3.3
作者：
ANDERSON, NB;ARMSTEAD, CA
通讯作者：
ARMSTEAD, CA