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：
10260560
负责人：
AMY MARGOLIS
金额：
$ 63.96万
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 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10260560
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

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

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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.

在子宫内双酚A（BPA）暴露破坏了动物和人类的神经行为发育。这子宫内BPA与神经行为发育中接触的途径可能涉及子宫内的直接影响婴儿脑发育和间接影响出生后母亲相互作用。父母社会行为可能尤其容易受到内分泌干扰化学物质（例如BPA）的影响行为是由荷尔蒙启动和社会/父母大脑的组织形成的。大多数人类文学确定了BPA对大孩子的影响，而对生命的第一年很少。在啮齿动物和灵长类动物模型，在子宫暴露于BPA中会破坏后代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对婴儿脑发育和注意力的直接影响，以及尚未检查通过BP引起的母亲相互作用的变化对这些影响的调节。我们因此，不知道BPA可能破坏发展的途径。虽然BPA已被删除从许多消费产品中，它已被结构类似物，双酚S（BPS）和Bisphenol-f取代（BPF），可能具有相似的有害影响。这项研究将：1）检查子宫内BP中的关联（综合暴露）暴露和婴儿的脑功能和注意力，2）进行平行的啮齿动物研究子宫内BP暴露对大脑细胞和分子变化的影响，3）翻译人类方法研究母亲相互作用以在我们的啮齿动物模型中使用并确定BP对这些的影响护理互动。在人类和啮齿还大脑和认知发育受BP诱导的母亲相互作用的变化来调节。在我们的翻译方法，我们在1个月和9个月招募婴儿，并评估婴儿的大脑功能和注意力在两个时间点，我们利用先前资助的母亲相互作用的测量来测试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BP暴露对后代皮质基因的表达，结构，注意力和母亲相互作用的质量。影响：此R01解决了我们对子宫内分泌中分类中如何暴露于子宫内的关键差距化学物质会改变婴儿的大脑和认知功能。了解这些影响对于发展至关重要筛查工具和干预措施，以对神经发育产生影响。 R01也提供在该团队的未来翻译合作中使用的初步数据。未来的动物研究将通过交叉促进实验来解除BP的直接和间接影响，人类研究将跟随该队列进入学龄，以研究BP诱导的神经发育影响的神经相关性。