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.

双酚A（BPA），存在于聚碳酸酯塑料、环氧树脂和无碳 在其它产品中，热接收几乎是普遍存在的。我们和其他人在一个范围内进行了大量的研究， 的物种已经表明，在发育的关键阶段，BPA暴露会改变社会性，情绪， 学习和记忆相关的行为引起了人们对BPA暴露的关注，特别是在怀孕期间， 早期生活，可能导致儿童和成人行为障碍的发病率增加。 由于迄今为止的大多数研究都不是专门设计来指导人类风险评估的， NTP/FDA对Sprague道利大鼠进行的慢性暴露研究，以表征围产期BPA暴露的方式 影响青少年和成年期的焦虑、记忆相关、交配和择偶行为 在三个与人类相关的剂量中，将产生关键数据，可以为公共政策提供有关潜在的 BPA对健康的影响这项拟议的研究将测试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程序， 改变表观遗传景观和随后的基因表达。Worl< in Aimi将建立影响， 妊娠期暴露对下丘脑和海马中遗传和表观遗传表达的影响 新生大鼠目标2中的研究将评估BPA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描述慢性BPA暴露如何影响 成年人的社会性和认知行为，并确定海马和下丘脑DNA 在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， 行为改变这些研究将提供关键的观察和机制的见解， 不早期暴露于BPA会以性别特异性方式增加行为异常的风险， 孩子