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）：在聚碳酸酯塑料，环氧树脂树脂和无碳热收益等中发现的双苯酚A（BPA）的人类接触几乎无处不在。在一系列物种中进行的许多研究表明，在临界窗口期间，BPA暴露会改变社交，情绪，学习和与记忆有关的行为，这引起人们担心BPA暴露，尤其是在妊娠和早期生活期间，可能会导致儿童和成人行为障碍的发生率增加。 因为迄今为止的大多数研究尚未专门设计用于指导人类风险评估，因此在Sprague Dawley大鼠中利用国家毒理学计划/食品和药物管理局（NTP/FDA）长期暴露研究，以表征围产期BPA暴露的表征，表征焦虑如何影响焦虑，记忆与群体相关，同伴的偏好在三个范围内的范围跨性别的疾病范围内的范围跨性别的人类范围的影响，而跨性别的人类跨性别的态度则构成了人类范围内的危害，而成年人的范围越来越多的人类实现人类范围内的人类范围的影响。 BPA。这些提出的研究将检验以下假设，即BPA通过改变性别特定的海马和下丘脑的发育节目来破坏行为反应，这可能通过改变表观遗传景观和随后的基因表达来破坏行为反应。 AIM 1中的工作将建立妊娠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。 AIM 2中的研究将评估BPA对性别和AIM 3中的焦虑，活动和与记忆相关的行为的影响。这些研究将对早期暴露于BPA是否会以儿童的性别特定方式增加行为异常的风险，从而提供关键的观察和机理见解。