Piloting a Novel Approach for Examining Intersecting Environmental Exposures and Social Behavior

试验一种检查交叉环境暴露和社会行为的新方法

基本信息

批准号：
10518668
负责人：
Heather B Patisaul
金额：
$ 7.6万
依托单位：
NORTH CAROLINA STATE UNIVERSITY RALEIGH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10518668
关键词：
Address Adverse event Air Pollution Animal Model Animals Anxiety Anxiety Disorders Behavior Behavioral Brain Breeding Caring Chemical Exposure Chemicals Child Child Health Childhood Chronic stress Communities Complement Complex Data Development Developmental Disabilities Diagnosis Disease Dose Electronics Environmental Exposure Environmental Pollution Experimental Designs Exposure to Face Fathers Feasibility Studies Female Flame Retardants Funding Furniture Future Generations Genetic Goals Human Impaired cognition Impairment Individual Infant Knowledge Life Link Mental disorders Microtus Modeling Motivation Mus Nature Neurobiology Neurodevelopmental Disorder Neurosecretory Systems Oral Outcome Pair Bond Perinatal Pilot Projects Plasticizers Poverty Prevalence Rattus Reproducibility Research Project Grants Risk Rodent Model Scheme Sex Bias Sex Differences Social Behavior Social Interaction Social isolation Stress Testing Tissues Toxicology United States National Institutes of Health Weight Work aged anxiety-related behavior autism spectrum disorder behavior test behavioral impairment boys brain behavior disorder risk early life adversity early life exposure environmental stressor experimental study exposed human population generalized anxiety girls innovation interest male novel novel strategies nutrition offspring personal care products pollutant postnatal prairie vole prenatal exposure preservation programs psychosocial relating to nervous system sex social social anxiety social deficits social stress stressor tool trait virtual

项目摘要

Project Summary/Abstract Rates of neurodevelopmental disorders (NDDs) are rapidly and inexplicably rising with one in six US children aged 3-17 diagnosed with a developmental disability between 2009 and 2017, and nearly 33% of US children aged 13-18 suffering from an anxiety disorder. Mental health disorders such as anxiety and autism spectrum disorder (ASD) manifest in each sex differently and can persist for a lifetime, thus understanding their origins is highly significant. Prenatal exposure to chemical pollutants such as air pollution, plasticizers, and flame retardants (FRs), are hypothesized to be one causal factor elevating NDD risk in both sexes. The available experimental data, however, testing this hypothesis is surprisingly minimal and discordant. Moreover, chemical exposures frequently occur in combination with other stressors known to heighten risk of psychosocial disorders including chronic stress and social isolation. Thus, understanding how multiple adverse environmental “hits” act in combination to exacerbate risk of socioemotional deficits is a critically important but unmet need. This project addresses the pressing need for rigorous, reproducible, human-relevant studies examining potential links between environmental exposures and social deficits common to many NDDs. We will use the prairie vole (Microtus ochrogaster), a well-established, pro-social animal model for exploring the neurobiology of ASD and other social disorders, but generally unfamiliar to toxicologists, to test the hypothesis that father absence during rearing will exacerbate known behavioral deficits induced by developmental exposure to the chemical flame retardant (FR) mixture FireMaster 550, (FM 550) particularly in male offspring. Unlike rats and mice, this species is monogamous and biparental and thus a uniquely suitable model for examining the impact of adverse events on social behavior. Our preliminary data in FM 550 exposed prairie voles reveal heightened anxiety in females and loss of pair bonding in males. The focus on FRs is significant because exposure to this chemical class has long been associated with behavioral and cognitive impairments in humans, including heightened risk of ASD, and human exposure is global and increasing. The proposed self-contained study builds on our prior work by using oral exposure to a human relevant dose, more refined testing strategies to better capture pair bonding behaviors, and the inclusion of father absence as a second adverse childhood exposure; a situation all too common in heavily polluted communities. This innovative, feasibility study is highly responsive to NIH interest in the “exposome” (chemical and experiential) as a driver of children's health. Through this small, defined project we hope to elucidate the impact of combined early life stressors on social traits of relevance to human NDDs in both sexes. Critically, the behavioral results gained from piloting the prairie vole as a powerful tool for toxicology paves the way for future work seeking to identify the mechanisms by which chemical exposures may contribute to the growing prevalence of NDDs in the context of the full exposome.

项目摘要/摘要神经发育障碍（NDD）的发生率迅速且莫名其妙地上升，其中六分之一的儿童在2009年至2017年之间被诊断出患有发育障碍的3-17岁，近33％的儿童 13-18岁患有焦虑症。心理健康障碍，例如焦虑和自闭症谱系疾病（ASD）在每种性别中表现出不同的表现，并且可以持续一生，因此了解它们的起源是产前暴露于化学污染物，例如空气污染，增塑剂和火焰粘贴剂（FRS）被认为是两性中NDD风险升高的因素之一。可用但是，实验数据检验该假设是惊人的最小和不一致的。而且，化学经常与其他已知的压力源结合发生的暴露量会增加心理障碍的风险包括慢性压力和社会隔离。这是了解多次不利环境“命中”行为结合加剧社会情感定义的风险是至关重要但未满足的需求。这个项目解决了严格，可重复的，与人相关的研究的紧迫需求，以研究潜在的联系在许多NDD共同的环境暴露与社会缺陷之间。我们将使用Prairie Vole（Microtus ochrogaster），这是一个完善的亲社会动物模型探索ASD和其他社会疾病的神经生物学，但通常不熟悉Te毒理学家，为了测试假设，即饲养过程中父亲的吸收会加剧已知的行为缺陷发育暴露于化学火焰（FR）混合物Firemaster 550（FM）引起的诱导 550）尤其是在男性后代。与大鼠和小鼠不同，该物种是一夫一妻制的，二聚会，因此一个独特的模型，用于研究不良事件对社会行为的影响。我们的初步数据在FM 550中，裸露的草原田鼠揭示了女性的动画增强，并且男性的成对结合丧失。这专注于FRS是重要的，因为对该化学类别的暴露长期与行为相关人类的认知障碍（包括ASD风险增加，人类暴露的风险增加）是全球性的，增加。拟议的独立研究是基于我们先前的工作，通过使用口腔接触人相关剂量，更精致的测试策略以更好地捕获配对键行为，并包括父亲缺席是第二次不利的儿童暴露；在严重污染的社区中，这种情况非常普遍。这项创新的，可行性的研究对NIH的反应很高，在“杂物”（化学和化学和经验）作为儿童健康的驱动力。通过这个小的，定义的项目，我们希望阐明影响早期的生活压力源与男女中与人类NDD相关的社会特征。至关重要的是通过将草原Vole作为毒理学的强大工具铺平了未来的道路，从而获得了行为结果寻求确定化学暴露可能导致不断增长的机制的工作在完整的展示体背景下的NDD。