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: 8230017
• 负责人: Heather B Patisaul
• 金额: $ 28.21万
• 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/8230017
• 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; National Toxicology Program; 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; United States Food and Drug Administration; 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

DESCRIPTION (provided by applicant): Human exposure to Bisphenol A (BPA), found in polycarbonate plastics, epoxy resins, and carbonless thermal receipts, among other products, is nearly ubiquitous. Numerous studies in a range of species have shown that BPA exposure during critical windows 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 National Toxicology Program/Food and Drug Administration (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. These 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. Work in aim 1 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.

描述（由申请人提供）：人体暴露于双酚A（BPA），在聚碳酸酯塑料、环氧树脂和无碳热接收器等产品中发现，几乎无处不在。在一系列物种中进行的大量研究表明，在发育的关键窗口期暴露于BPA会改变社会性行为、情绪、学习和记忆相关行为，这引起了人们的关注，特别是在妊娠期和生命早期，BPA暴露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不是专门设计用于指导人类风险评估，因此利用国家毒理学计划/食品和药物管理局（NTP/FDA）在Sprague道利大鼠中进行的慢性暴露研究来表征围产期BPA暴露如何影响焦虑，记忆相关，交配和择偶偏好行为在青少年和成年生活在三个人类-相关剂量将产生关键数据，可以为有关BPA潜在健康影响的公共政策提供信息。这些拟议的研究将测试BPA通过改变海马和下丘脑的性别特异性发育程序来破坏行为反应的假设，可能是通过改变表观遗传景观和随后的基因表达。目标1的工作将确定妊娠期暴露对新生大鼠下丘脑和海马中遗传和表观遗传表达的影响。目标2中的研究将评估BPA对青少年焦虑、活动和记忆相关行为的影响，目标3中的工作将描述慢性BPA暴露如何影响成年人的社会性行为和认知行为，并确定新生儿生命中观察到的海马和下丘脑DNA甲基化和基因表达变化是否是永久性的，并与观察到的行为变化相关。这些研究将为早期暴露于BPA是否会以性别特异性方式增加儿童行为异常的风险提供关键的观察和机制见解。