Neurobehavioral effects of Bisphenol A Across age and sex

人体接触双酚A(BPA)，存在于聚碳酸酯塑料、环氧树脂和无碳树脂中 在其他产品中，热敏收据几乎无处不在。我们和其他人在一系列研究中进行的大量研究 已经表明，在发育的关键时期暴露于双酚A会改变社会性行为，情绪， 与学习和记忆相关的行为引起了人们的关注，双酚A接触，特别是在怀孕和 早年生活，可能是导致儿童和成人行为障碍发生率增加的原因之一。 因为到目前为止，大多数研究都不是专门为指导人类风险评估而设计的，利用 NTP/FDA慢性暴露SD大鼠研究围产期BPA暴露的特征 影响青少年和成年人的焦虑、记忆相关、交配和择偶行为 三种与人体相关的剂量将产生关键数据，这些数据可以为公共政策提供有关潜在的 双酚A对健康的影响。这项拟议的研究将检验双酚A干扰行为反应的假设 通过改变海马体和下丘脑的性别特异性发育程序，可能是通过 改变表观遗传格局和随后的基因表达。世界将在爱米建立影响 孕期暴露对小鼠下丘脑和海马区遗传和表观遗传表达的影响 新生的老鼠。Aim 2的研究将评估双酚A对焦虑、活动和记忆相关的影响 在目标3中工作的男女青少年的行为将表征长期接触双酚A如何影响 成人的社会性行为和认知行为，并确定海马体和下丘脑的DNA 新生儿生活中出现的甲基化和基因表达变化是永久性的，并与观察到的 行为上的改变。这些研究将提供关键的观察性和机械性的见解，无论是 不及早暴露于双酚A会以性别特有的方式增加行为异常的风险 孩子们。

Human exposure to Bisphenol A (BPA), found in polycarbonate plastics, epoxy resins, and carbonless thermal receipts, among other products, is nearly ubiquitous. Numerous studies by us and others in a range of species have shown that BPA exposure during critical windov\/s of development alters sociosexual, mood, learning and memory-related behaviors raising concern that BPA exposure, particularly during gestation and early life, might be contributing to increased incidences of behavioral disorders in children and adults. Because most studies to date were not specifically designed to guide human risk assessment, leveraging the NTP/FDA chronic exposure study in Sprague Dawley rats to characterize how perinatal BPA exposure affects anxiety, memory-related, copulatory and mate preference behaviors during juvenile and adult life across three human-relevant doses will yield critical data that can inform public policy regarding the potential health effects of BPA. This proposed studies will test the hypothesis that BPA disrupts behavioral responses by altering sex specific developmental programming of the hippocampus and hypothalamus, potentially by altering the epigenetic landscape and subsequent gene expression. Worl< in Aimi will establish the impact of gestational exposure on genetic and epigenetic expression in the hypothalamus and hippocampus of newborn rats. Studies in Aim 2 will evaluate the effects of BPA on anxiety, activity and memory-related behaviors in juveniles of both sexes and work in Aim 3 will characterize how chronic BPA exposure affects sociosexual and cognitive behavior in adults, and determine if hippocampal and hypothalamic DNA methylation and gene expression changes seen in neonatal life are permanent and correlate with observed behavioral changes. These studies will provide critical observational and mechanistic insights into whether or not early exposure to BPA increases the risk for behavioral abnormalities in a sex-specific manner in children.