Neurobehavioral effects of Bisphenol A Across age and sex

双酚 A 对不同年龄和性别的神经行为影响

• 批准号: 8334569
• 负责人: Heather B Patisaul
• 金额: $ 19.65万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-19 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8334569
• 关键词: Adolescent; Adult; Affect; Age; Anxiety; Attention deficit hyperactivity disorder; Behavior; Behavior Disorders; Behavior assessment; Behavioral; Birth; Brain; Brain region; Brain-Derived Neurotrophic Factor; Candidate Disease Gene; Chemicals; Child; Chronic; Cognitive; Cues; DNA Methylation; Data; Dental Materials; Development; Disease; Dopamine Receptor; Dose; Elements; Endocrine Disruptors; Epigenetic Process; Epoxy Resins; Etiology; Exposure to; Female; Gene Expression; Gene Expression Profile; Generalized Anxiety Disorder; Genes; Genetic; Glucocorticoid Receptor; Goals; Health; Hippocampus (Brain); Household; Human; Hyperactive behavior; Hypothalamic structure; Incidence; Instruction; Lead; Learning; Life; Longevity; Mediating; Memory; Mental disorders; Methylation; Molecular; Moods; Motor Activity; Neonatal; Newborn Infant; Outcome; Partner in relationship; Pattern; Perinatal; Perinatal Exposure; Plastics; Pregnancy; Prevalence; Production; Puberty; Public Policy; Rattus; Reverse Transcriptase Polymerase Chain Reaction; Risk; Risk Assessment; Rodent; Severities; Sex Behavior; Sex Bias; Sex Characteristics; Shapes; Short-Term Memory; Sprague-Dawley Rats; Symptoms; Testing; Visuospatial; Weaning; Work; behavioral deficiency; bisphenol A; design; exposed human population; fitness; insight; mRNA Expression; male; neonate; neurobehavioral; neuromechanism; nonhuman primate; polycarbonate plastic; preference; prenatal; programs; prospective; response; sex; steroid hormone receptor; way finding

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.

人类接触聚碳酸酯塑料、环氧树脂和无碳碳酸酯中的双酚 A (BPA) 除其他产品外，热敏收据几乎无处不在。我们和其他人在一系列领域进行了大量研究 的物种表明，在发育的关键时期接触 BPA 会改变社会性、情绪、 与学习和记忆相关的行为引起人们对双酚 A 暴露的关注，特别是在妊娠期和 早年生活可能会导致儿童和成人行为障碍的发生率增加。 由于迄今为止的大多数研究并不是专门为指导人类风险评估而设计的，因此利用 NTP/FDA 对 Sprague Dawley 大鼠进行慢性暴露研究，以描述围产期 BPA 暴露的特征 影响青少年和成年生活中的焦虑、记忆相关、交配和择偶行为 跨越三种与人类相关的剂量将产生关键数据，可以为有关潜在风险的公共政策提供信息 BPA 对健康的影响。这项拟议的研究将检验 BPA 扰乱行为反应的假设 通过改变海马体和下丘脑的性别特异性发育编程，可能通过 改变表观遗传景观和随后的基因表达。世界<在艾米将建立的影响 妊娠暴露对下丘脑和海马遗传和表观遗传表达的影响 新生大鼠。目标 2 的研究将评估 BPA 对焦虑、活动和记忆相关的影响 目标 3 中男女青少年的行为和工作将描述长期 BPA 暴露如何影响 成人的社会性行为和认知行为，并确定海马和下丘脑 DNA 是否 新生儿生命中观察到的甲基化和基因表达变化是永久性的，并且与观察到的相关 行为改变。这些研究将为是否或 不及早接触 BPA 会增加特定性别行为异常的风险 孩子们。