Environmental bisphenol exposure, infant brain and behavior: Human and animal models

环境双酚暴露、婴儿大脑和行为：人类和动物模型

基本信息

批准号：
10064434
负责人：
AMY MARGOLIS
金额：
$ 67.18万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-10 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10064434
关键词：
Address Animal Model Animals Anxiety Attention Attention deficit hyperactivity disorder Auditory Behavior Behavioral Biometry Birth Brain Caring Child Code Cognition Cognitive Collaborations DNA Methylation Data Detection Development Electroencephalography Emotional Endocrine Disruptors Environment Environmental Health Epigenetic Process Event-Related Potentials Exposure to Fetus Follow-Up Studies Fostering Frequencies Funding Future Gene Expression Goals Hormonal Human Impairment Individual Differences Infant Infant Development Infrastructure Intervention Knowledge Lead Life Link Literature Maternal Behavior Measurement Measures Mediating Medical center Methods Midbrain structure Modeling Molecular Molecular Structure Mothers N-Methyl-D-Aspartate Receptors Nervous System Physiology Neuraxis Neurodevelopmental Deficit Neurodevelopmental Disorder Neurosciences Neurosecretory Systems Neurotoxins Outcome Pathway interactions Pregnant Women Primates Risk Rodent Rodent Model Role School-Age Population Science Screening procedure Sensory Sensory Process Signal Transduction Social Behavior Social Development Structure Testing Texas Time Translating Universities Variant Visual age related analog anxiety-like behavior attentional modulation austin bisphenol A brain behavior caregiving cognitive development cognitive function cohort consumer product cost density dopaminergic neuron experimental study exposed human population fetal human model improved in utero indexing maternal caregiving multisensory neural circuit neural correlate neurobehavioral neurodevelopment neurodevelopmental effect neuroimaging neurophysiology neurotoxicology novel offspring postnatal prenatal exposure public health intervention receptor binding recruit relating to nervous system social organization translational approach virtual

项目摘要

In utero bisphenol A (BPA) exposure disturbs neurobehavioral development in animals and in humans. The pathways linking in utero BPA exposure to neurobehavioral development likely involve direct effects in utero on infant brain development, and indirect effects via disruption of postnatal mother-infant interactions. Parental social behaviors may be especially vulnerable to endocrine-disrupting chemicals such as BPA as these behaviors are shaped by hormonal priming and by the organization of the social/parental brain. Most of the human literature identifies effects of BPA in older children, with little focus on the first year of life. In rodent and primate models, in utero exposure to BPA disrupts offspring cognitive and social development and maternal care via epigenetic changes. In humans, the direct effect of BPA on infant brain development and attention, and the modulation of these effects by BP-induced changes to mother-infant interaction, have not been examined. We thus do not know the pathways through which BPA may disrupt development. Although BPA has been removed from many consumer products, it has been replaced by structural analogs, bisphenol-s (BPS) and bisphenol-f (BPF), which may have similar detrimental effects. This study will: 1) examine associations between in utero BP (combined exposure) exposure and infant brain function and attention, 2) conduct a parallel rodent study of the effects of in utero BP exposure on cellular and molecular changes in the brain, and 3) translate a human method of studying mother-infant interaction for use in our rodent model and determine the effects of BP on these caregiving interactions. In both humans and rodents, we ask whether associations detected between in utero BP and brain and cognitive development are moderated by BP-induced change in mother-infant interaction. In our translational approach, we recruit infants at 1- and 9-months old and assess infant brain function and attention at two timepoints, and we leverage previously funded measurement of mother-infant interaction to test its moderating effects on these associations. In our parallel rodent model, we measure effects of BP exposure on offspring cortical gene expression, structure, attention and quality of mother-infant interactions. Impact: This R01 addresses a critical gap in our understanding of how in utero exposure to endocrine-disrupting chemicals alters infant brain and cognitive function. Understanding these effects is essential to developing screening tools and intervention for downstream effects on neurodevelopment. The R01 also provides preliminary data for use in future translational collaborations among this team. Future animal studies will disentangle the direct and indirect effects of BP through cross-fostering experiments, and human studies will follow this cohort into school age to investigate neural correlates of BP-induced effects on neurodevelopment.

子宫内双酚 A (BPA) 暴露会扰乱动物和人类的神经行为发育。这子宫内 BPA 暴露与神经行为发育之间的联系途径可能涉及子宫内的直接影响婴儿大脑发育，以及通过破坏产后母婴互动而产生的间接影响。家长社会行为可能特别容易受到 BPA 等内分泌干扰化学物质的影响，因为行为是由荷尔蒙启动和社会/父母大脑的组织塑造的。大部分的人类文献确定了 BPA 对年龄较大儿童的影响，但很少关注生命的第一年。在啮齿动物和灵长类动物模型，在子宫内接触 BPA 会扰乱后代的认知和社会发展以及孕产妇护理通过表观遗传变化。在人类中，BPA 对婴儿大脑发育和注意力的直接影响，以及血压引起的母婴互动变化对这些影响的调节尚未得到研究。我们因此不知道 BPA 可能通过哪些途径破坏发育。虽然 BPA 已被去除在许多消费品中，它已被结构类似物双酚-s (BPS) 和双酚-f 所取代（BPF），可能具有类似的有害影响。这项研究将：1）检查子宫内血压之间的关联（组合暴露）暴露与婴儿脑功能和注意力，2）进行平行啮齿动物研究子宫内血压暴露对大脑细胞和分子变化的影响，3) 转化人类方法研究用于我们的啮齿动物模型的母婴互动并确定血压对这些的影响护理互动。在人类和啮齿动物中，我们询问是否在子宫内血压之间检测到关联大脑和认知发展受到血压引起的母婴互动变化的调节。在我们的转化方法，我们招募 1 个月和 9 个月大的婴儿并评估婴儿的大脑功能和注意力在两个时间点，我们利用之前资助的母婴互动测量来测试其对这些关联的调节作用。在我们的平行啮齿动物模型中，我们测量了血压暴露对后代皮质基因表达、结构、注意力和母婴互动的质量。影响：R01 解决了我们对子宫内如何接触内分泌干扰物的理解上的一个关键差距化学物质会改变婴儿的大脑和认知功能。了解这些影响对于开发至关重要筛选工具和干预对神经发育的下游影响。 R01还提供用于该团队未来翻译合作的初步数据。未来的动物研究将通过交叉培养实验理清血压的直接和间接影响，人体研究将跟踪这个队列进入学龄期，以研究血压引起的神经发育影响的神经相关性。