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.

遗传和内分泌因子与多动注意力缺陷障碍的病因有关 （多动症）。多氯联苯（PCB），我们建议多溴二苯基醚（PBDES） 在发育暴露的儿童以及 降低实验动物中的中央儿茶酚胺和甲状腺激素水平？生理变化 也可以在多动症中看到。我们假设由于其能力而对PCB和PBDES的发展暴露 在关键时期改变中央儿茶酚胺和/或甲状腺激素是病因 负责污染物引起的行为变化的因素，这让人联想到那些 多动症。更好地了解这些行为改变的生理基础，并获得见解 ADHD的病因我们将确定：（i）这些污染物单独和联合的影响 中央儿茶酚胺以及孕产妇和后代循环甲状腺激素水平； （ii）是否 孕产妇和胎儿循环甲状腺激素（用甲唑诱导）的实验减少模仿 与PCB和/或PBDE的中央儿茶酚胺中看到的变化； （iii）是否引起污染物 补充母亲T4或 成人哌醋甲酯暴露和（iv）这些操纵对mRNA表达和 调节前额叶皮质，纹状体和海马中调节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结合在一起时，将开始确定 这些污染物改变行为的机制使人联想到发育中的多动症 儿童，包括污染物诱发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展并最终行为方面起作用。