Developmental Neuroendocrine Effects of PCBs and PBDEs: Parallels with ADHD

PCB 和 PBDE 对发育神经内分泌的影响：与 ADHD 的相似之处

• 批准号: 7282306
• 负责人: Richard Field Seegal
• 金额: $ 28.62万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-25 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7282306
• 关键词: attention deficit disorder; behavioral /social science research tag; catecholamines; child psychology; developmental neurobiology; dietary supplements; disease /disorder etiology; disease /disorder model; endocrine pharmacology; environmental contamination; environmental exposure; gene expression; halobiphenyl /halotriphenyl compound; hormone therapy; hypothyroidism; imidazole; laboratory rat; messenger RNA; methylphenidate; mother /embryo /fetus nutrition; neurochemistry; neuroendocrine system; neurotoxicology; nutrition related tag; thyroxine

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.

遗传和内分泌因素与注意缺陷多动障碍的病因有关 (ADHD)。多氯联苯(PCbs)，以及我们建议的多溴二苯醚(PBDEs) 在发育中暴露的儿童中导致类似的注意力和冲动控制缺陷，以及 降低实验动物中枢儿茶酚胺和甲状腺激素水平的生理变化 也可见于ADHD。我们假设发育过程中暴露于多氯联苯和多溴二苯醚，由于它们的能力 在发育的关键时期改变中枢儿茶酚胺和/或甲状腺激素是病因。 导致污染物引起的行为变化的因素让人想起在 多动症。为了更好地了解这些行为改变的生理基础，并获得对 我们将确定ADHD的病因：(I)这些污染物单独和联合对 中枢儿茶酚胺与母子循环甲状腺激素水平； 母体和胎儿循环甲状腺激素(他巴唑诱导)减少的实验模拟 中枢儿茶酚胺与多氯联苯和/或多溴二苯醚的变化；(Iii)是否由污染物引起 中枢儿茶酚胺的减少可以在母亲补充T4或 成人暴露的哌醋甲酯和(Iv)这些操作对mRNA表达和 调节前额叶皮质、纹状体和海马儿茶酚胺功能的蛋白质。这些研究， 当与类似暴露的动物的行为数据相结合时，将开始确定 这些污染物改变发育过程中易患ADHD的行为的机制 儿童，包括污染物导致中枢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了作用。