Bisphenol A Effect on Primate Brain

双酚 A 对灵长类动物大脑的影响

基本信息

批准号：
7885238
负责人：
CSABA LERANTH
金额：
$ 71.08万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-06 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7885238
关键词：
Address Adolescent Adult Adverse effects Affect Affinity Animals Area Attention Behavior Beverages Biological Brain Bypass Canned Foods Chemicals Child Cognition Cognitive Data Dependency Development Dopamine Dose Endocrine system Environment Environmental Policy Epoxy Resins Equipment Estradiol Estrogen Nuclear Receptor Exposure to Female Food Food Container Future Gonadal Steroid Hormones Grant Guidelines Health Hippocampus (Brain)Hormones Human Impaired cognition Infant Ingestion Institution Intake Iris Learning Long-Term Effects Measurement Mediating Memory Mental Depression Modeling Monkeys National Toxicology Program Nature Oral Performance Perinatal Pit and Fissure Sealants Plastics Play Prefrontal Cortex Primates Prosthesis Publishing Rattus Recommendation Reporting Research Retrieval Risk Rodent Rodent Model Role Route Safety Stimulus Stress Suggestion Synapses System Testing Testosterone Time Toxicology United States Environmental Protection Agency United States Food and Drug Administration Vertebral column Withdrawal base bisphenol A brain morphology cognitive function depressive symptoms design drinking exposed human population falls male mimetics monoamine neurochemistry neuron development neuronal circuitry neurotransmission nonhuman primate polycarbonate polycarbonate plastic postnatal prenatal prevent public health relevance reproductive research study response subcutaneous synaptogenesis xenoestrogen

项目摘要

DESCRIPTION (provided by applicant): Bisphenol A (BPA) is an estrogenic chemical that is widely used in the manufacture of polycarbonate plastics and epoxy resins. Because BPA leaches out of plastic food and drink containers and baby bottles, there is a wide human exposure to this compound. We have demonstrated for the first time that low-dose BPA treatment of gonadectomized female and male rats and monkeys inhibits the synaptogenic effect of sex steroids in the hippocampus and prefrontal cortex. Mounting evidence indicates that remodeling of hippocampal and prefrontal spine synapses is a morphological basis for learning and memory, suggesting that the negative synaptogenic effects of BPA are associated with impaired cognitive performance. According to the National Toxicology Program, available evidence provides a basis for concern, yet the Food and Drug Administration (FDA) concludes that data collected so far is not sufficient to resolve the problem whether BPA exposure represents a threat to human health. The FDA calls for further studies on BPA that are more relevant to human health. In this application, we propose three specific aims that are designed along guidelines published in the most recent FDA report on BPA. Using our established nonhuman primate model, we will test the hypothesis that BPA- induced loss of hippocampal and prefrontal spine synapses and compromised dopaminergic neurotransmission are associated with impaired cognitive performance. In addition, we will analyze whether the effects of BPA are cumulative and whether they are reversible. Finally, infants and children in particular seem to be at the highest level of risk from BPA exposure, because low- dose BPA interferes with neuronal development in rodents, leading to potentially irreversible alterations in behavior. Our last specific aim is designed to address this problem by analyzing whether perinatal BPA exposure causes irreversible harm in our nonhuman primate model. These studies will provide information on the risks of BPA exposure with most relevance to human health, which will be highly valuable for governing bodies to appropriately regulate the use of BPA. PUBLIC HEALTH RELEVANCE: Recent rodent studies suggest that the xenoestrogen, bisphenol A, at levels found in the environment, is capable of diminishing one's ability to learn and interferes with brain development. Because there are considerable differences between the brains of rodents and humans, this suggestion is intensively debated. Therefore, we will investigate how bisphenol A affects the brain and learning capability of adult and juvenile monkeys, to provide results that are more relevant to human health and may guide future environmental policy about bisphenol A.

描述（由申请人提供）：双酚A（BPA）是一种雌激素化学物质，可广泛用于多碳酸盐塑料和环氧树脂的生产中。由于BPA从塑料食品和饮料容器和婴儿瓶中浸出，因此人类对这种化合物有广泛的曝光。我们首次证明了对雌性和雄性大鼠和猴子的低剂量BPA治疗抑制性类固醇在海马和前额叶皮层中的突触。越来越多的证据表明，海马和前脊柱突触的重塑是学习和记忆的形态学基础，这表明BPA的负突触作用与认知性能受损有关。根据国家毒理学计划，现有证据为人们提供了基础，但是食品药品监督管理局（FDA）得出结论，到目前为止收集的数据不足以解决问题，是否对BPA暴露是否代表了对人类健康的威胁。 FDA要求对BPA进行进一步研究，这些研究与人类健康更相关。在此应用程序中，我们提出了三个符合FDA关于BPA的FDA报告中发布的指南的三个特定目标。使用我们已建立的非人类灵长类动物模型，我们将检验以下假设：BPA诱导的海马和前脊椎突触的丧失以及受损的多巴胺能神经传递与认知性能受损有关。此外，我们将分析BPA的影响是否是累积的以及它们是否可逆。最后，尤其是婴儿和儿童似乎处于BPA暴露的最高风险，因为低剂量BPA会干扰啮齿动物的神经元发育，从而导致行为的可能不可逆的改变。我们的最后一个特定目标旨在通过分析围产期BPA暴露是否在我们的非人类灵长类动物模型中造成不可逆转的伤害来解决这一问题。这些研究将提供有关BPA暴露风险以及与人类健康最相关的信息，这对于管理机构可以适当调节BPA的使用非常有价值。公共卫生相关性：最近的啮齿动物研究表明，在环境中发现的水平上的异源雌激素A Bisphenol A能够降低一个人的学习能力和干扰脑发育。因为啮齿动物和人类的大脑之间存在很大的差异，所以这一建议是有争议的。因此，我们将研究双酚A如何影响成年和少年猴子的大脑和学习能力，以提供与人类健康更相关的结果，并可能指导有关双酚A的未来环境政策。