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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.

项目总结/文摘