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多动注意力缺陷障碍的病因有关 （多动症）。多氯联苯 (PCB) 和我们建议的多溴二苯醚 (PBDE) 在发育中暴露的儿童中引起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？生理变化 也见于多动症。我们假设，由于多氯联苯和多溴二苯醚的能力，发育过程中接触多氯联苯和多溴二苯醚 在发育的关键时期改变中枢儿茶酚胺和/或甲状腺激素，是病因学 导致污染物引起的行为变化的因素让人想起那些在 多动症。为了更好地了解这些行为改变的生理基础并深入了解 为了确定 ADHD 的病因，我们将确定：(i) 这些污染物单独或联合使用对人体的影响 中枢儿茶酚胺和母体和后代循环甲状腺激素水平； (二) 是否 母体和胎儿循环甲状腺激素的实验性减少（用甲硫咪唑诱导）模拟 中心儿茶酚胺与 PCB 和/或 PBDE 的变化； (iii) 是否由污染物引起 母体补充 T4 后或可改善中枢儿茶酚胺的减少 成人哌醋甲酯暴露以及 (iv) 这些操作对 mRNA 表达的影响和 调节前额皮质、纹状体和海马中儿茶酚胺功能的蛋白质。这些研究， 当与类似暴露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暴露中的多动症行为的机制 儿童，包括污染物导致中心儿茶酚胺减少的相对贡献 甲状腺激素水平会改变神经系统发育并最终改变行为。