Developmental Neuroendocrine Effects of PCBs and PBDEs: Parallels with ADHD

遗传和内分泌因素与注意缺陷障碍伴多动的病因有关 （ADHD）。多氯联苯（PCBs）和我们建议的多溴联苯醚（PBDEs） 在发育中暴露的儿童中诱导类似的注意力和冲动控制缺陷，以及 降低实验动物的中枢儿茶酚胺和甲状腺激素水平？生理变化 也可以在ADHD中看到。我们假设，由于多氯联苯和多溴二苯醚的能力， 在发育的关键时期改变中枢儿茶酚胺和/或甲状腺激素， 导致污染物引起的行为变化的因素， 多动症。为了更好地理解这些行为改变的生理基础， ADHD的病因，我们将确定：（一）这些污染物的影响，单独和组合， 中央儿茶酚胺和母亲和后代循环甲状腺激素水平;（ii）是否 母体和胎儿循环甲状腺激素的实验性降低（用甲巯咪唑诱导）模拟 多氯联苯和/或多溴联苯醚引起的中央儿茶酚胺变化;（三）污染物是否引起 在母体补充T4或补充T4后， 成人哌甲酯暴露和（iv）这些操作对mRNA表达的影响， 调节前额叶皮层、纹状体和海马体中儿茶酚胺功能的蛋白质。这些研究， 当结合类似暴露动物的行为数据时，将开始确定 这些污染物改变行为的机制让人联想到ADHD在发育暴露 儿童，包括污染物引起的中央儿茶酚胺减少的相对贡献 甲状腺激素水平在改变神经系统发育和最终行为方面发挥作用。

Genetic and endocrine factors are implicated in the etiology of attention deficit disorder with hyperactivity (ADHD). Polychlorinated biphenyls (PCBs) and, we suggest, polybrominated diphenyl ethers (PBDEs) induce similar deficits in attention and impulse control in developmentally exposed children, as well as reducing central catecholamine and thyroid hormone levels in experimental animals?physiological changes also seen in ADHD. We hypothesize that developmental exposure to PCBs and PBDEs, due to their ability to alter central catecholamines and/or thyroid hormones during critical periods of development, are etiologic factors responsible for the contaminant induced behavioral changes that are reminiscent of those seen in ADHD. To better understand the physiological bases for these behavioral alterations and to gain insights to the etiology of ADHD we will determine: (i) the effects of these contaminants, alone and in combination, on central catecholamines and maternal and offspring circulating thyroid hormone levels; (ii) whether experimental reductions in maternal and fetal circulating thyroid hormones (induced with methimazole) mimic the changes seen in central catecholamines with PCBs and/or PBDEs; (iii) whether contaminant-induced reductions in central catecholamines can be ameliorated following either maternal T4 supplementation or adult methylphenidate exposure and (iv) the effects of these manipulations on mRNA expression and proteins that regulate catecholamine function in prefrontal cortex, striatum and hippocampus. These studies, when combined with behavioral data from similarly exposed animals, will begin to determine the mechanisms by which these contaminants alter behaviors reminiscent of ADHD in developmentally exposed children, including the relative contributions that contaminant induced reductions in central catecholamines and thyroid hormone levels play in altering nervous system development and ultimately behavior.