Lifetime consequences of combined maternal lead and stress
Lifetime consequences of combined maternal lead and stress
复制标题
DOI：
10.1111/j.1742-7843.2007.00189.x
复制
发表时间：
2008-02-01
影响因子：
3.1
通讯作者：
Weston, Douglas
中科院分区：
文献类型：
--
作者：
Cory-Slechta, Deborah A.;Virgolini, Miriam B.;Weston, Douglas
高铅暴露和高压力都针对社会经济地位低的人群。两者也作用于下丘脑-垂体-肾上腺（HPA）轴。铅通过影响中脑皮质边缘多巴胺通路破坏认知。应激激素通过HPA轴作用于相同的途径。事实上，铅和压力可能是相互作用的危险因素，作为我们实验室一系列研究的基本原理。这些表明，压力可以修改铅的影响，铅可以修改应激反应，值得注意的是，铅+应激效应可以发生在没有单独的影响，在大鼠。此外，母亲只有铅暴露可以永久改变基础皮质酮水平，应激反应（即永久修改HPA轴功能）和脑儿茶酚胺在两种性别的后代。铅+压力的相互作用不仅限于早期发展：甚至铅曝光开始断奶后改变基础皮质酮和应激反应。结果不同的性别，大脑区域，压力和测量时间，铅+压力相互作用复杂。改变HPA轴功能可能作为一种机制的行为和儿茶酚胺神经毒性与铅，以及与低社会经济地位的疾病和功能障碍的发病率增加。产妇铅暴露的永久性后果表明，铅筛查计划应包括孕妇铅暴露升高的风险，压力应被视为一个额外的风险因素。铅+压力的影响，观察到的风险因素单独的情况下，提出了问题的能力，目前的危害识别方法，以充分确定人类健康的神经毒物造成的风险。
Elevated lead (Pb) exposure and high stress both target low socio-economic status populations. Both also act on the hypothalamic-pituitary-adrenal (HPA) axis. Pb disrupts cognition through effects on the mesocorticolimbic dopamine pathway. Stress hormones act on this same pathway via the HPA axis. The fact that Pb and stress are likely interactive risk factors served as the rationale for a series of studies in our laboratory. These demonstrate that stress can modify Pb effects, that Pb can modify stress responsivity, and, notably, that Pb + stress effects can occur in the absence of an effect of either alone in rats. Furthermore, maternal only Pb exposure can permanently alter basal corticosterone levels, stress responsivity (i.e. permanent modification of HPA axis function) and brain catecholamines in offspring of both genders. Interactive effects of Pb + stress are not limited to early development: even Pb exposures initiated post-weaning alter basal corticosterone and stress responsivity. Outcomes differ in relation to gender, brain region, stressor and time of measurement, making Pb + stress interactions complex. Altered HPA axis function may serve as a mechanism for the behavioural and catecholaminergic neurotoxicity associated with Pb, as well as for the increased incidence of disease and dysfunctions associated with low socio-economic status. The permanent consequences of maternal only Pb exposure suggest that Pb screening programmes should include pregnant women at risk for elevated Pb exposure, and that stress should be considered as an additional risk factor. Pb + stress effects observed in the absence of either risk factor alone raise questions about the capacity of current hazard identification approaches to adequately identify human health risks posed by neurotoxicants.