Graham Devon L, Grace Curtis E, Braun Amanda A, Schaefer Tori L, Skelton Matthew R, Tang Peter H, Vorhees Charles V, Williams Michael T
Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, OH 45229-3039, USA.
Int J Dev Neurosci. 2011 Feb;29(1):45-55. doi: 10.1016/j.ijdevneu.2010.09.008. Epub 2010 Oct 8.
Despite restrictions, exposure to lead (Pb) continues. Moreover, exposure varies and is often higher in lower socioeconomic status (SES) families and remains a significant risk to cognitive development. Stress is another risk factor. Lower SES may be a proxy for stress in humans. When stress and Pb co-occur, risk may be increased. A few previous experiments have combined Pb with intermittent or acute stress but not with chronic stress. To determine if chronic developmental stress affects outcome in combination with Pb, we tested such effects on growth, organ weight, brain monoamines, and response to an acute stressor. Sprague Dawley rats were gavaged with Pb acetate (1 or 10 mg/kg) or vehicle every other day from postnatal day (P)4-29 and reared in standard or barren cages. Subsets were analyzed at different ages (P11, 19, 29). Chronic stress did not alter blood Pb levels but altered HPA axis response during early development whereas Pb did not. Pb treatment and rearing each altered organ-to-body weight ratios, most notably of thymus weights. Both Pb and rearing resulted in age- and region-dependent changes in serotonin and norepinephrine levels and in dopamine and serotonin turnover. The model introduced here may be useful for investigating the interaction of Pb and chronic developmental stress.
尽管存在限制,但铅(Pb)暴露仍在继续。此外,暴露情况各不相同,在社会经济地位较低(SES)的家庭中往往更高,并且仍然是认知发展的重大风险。压力是另一个风险因素。较低的社会经济地位可能是人类压力的一个指标。当压力和铅同时出现时,风险可能会增加。之前的一些实验将铅与间歇性或急性压力相结合,但没有与慢性压力相结合。为了确定慢性发育压力与铅共同作用是否会影响结果,我们测试了其对生长、器官重量、脑单胺以及对急性应激源反应的影响。从出生后第(P)4天至29天,每隔一天给斯普拉格-道利大鼠灌胃醋酸铅(1或10毫克/千克)或赋形剂,并将其饲养在标准或贫瘠的笼子里。在不同年龄(P11、19、29)对亚组进行分析。慢性压力并未改变血铅水平,但在早期发育过程中改变了下丘脑-垂体-肾上腺(HPA)轴反应,而铅则没有。铅处理和饲养方式各自改变了器官与体重的比例,最显著的是胸腺重量。铅和饲养方式都导致了血清素和去甲肾上腺素水平以及多巴胺和血清素周转率的年龄和区域依赖性变化。这里介绍的模型可能有助于研究铅与慢性发育压力的相互作用。