Prospective Evaluation of Air Pollution, Cognition, and Autism from Birth Onward

从出生起对空气污染、认知和自闭症的前瞻性评估

• 批准号: 9028828
• 负责人: HEATHER E VOLK
• 金额: $ 42.2万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-10 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9028828
• 关键词: Address; Affect; Air Pollutants; Air Pollution; Animal Model; Animals; Aromatic Polycyclic Hydrocarbons; Autistic Disorder; Behavior; Biological; Birth; Blood; Brain; Caliber; California; Child; Cognition; Cognitive deficits; Collaborations; DNA Methylation; Data; Development; Developmental Delay Disorders; Environment; Environmental Exposure; Environmental Health; Environmental Risk Factor; Epidemiologic Studies; Epidemiology; Epigenetic Process; Evaluation; Exhibits; Exposure to; Faculty; Family Study; Finches; Fostering; Funding; Future; Gene Expression; Genes; Genetic; Genetic Predisposition to Disease; Genetic Transcription; Genetic Variation; Genotype; Gerontology; Human; Human Resources; Infant; Investigation; Joints; Knowledge; Life; Measures; Mus; Parents; Particulate Matter; Phenotype; Predisposition; Pregnancy; Prospective Studies; Public Health Schools; Reporting; Research; Research Personnel; Resources; Risk; Schools; Structure; Tissues; Twin Studies; Umbilical Cord Blood; United States National Institutes of Health; Universities; Work; ambient air pollution; animal data; animal population study; autism spectrum disorder; base; behavior change; data modeling; early life exposure; exome; frontal lobe; gene environment interaction; genome wide association study; high risk; human data; in vivo Model; insight; medical schools; nanoscale; neurodevelopment; neurotoxic; particle; peripheral blood; prenatal; prenatal exposure; programs; prospective; public health intervention; public health relevance; response; transcriptome sequencing; transcriptomics; virtual

 DESCRIPTION (provided by applicant): This proposal seeks to establish a Virtual Consortium for Translational/Transdisciplinary Environmental Research (ViCTER) to build the investigative expertise to study the mechanism underlying established air pollution associations for Autism Spectrum Disorder (ASD) though complimentary mouse and epidemiologic studies. We build on the first prospective R01 (R01 ES023780) evaluating the relationship between prenatal air pollutant exposures, cognitive deficits, and ASDs. Our team and others have previously reported increased risk of ASD based on living near freeways, exposure to near roadway air pollution (NRAP), and to increasing levels of particulate matter less than 2.5 microns in diameter (PM2.5) during gestation. However, few studies have examined joint effects of the environment and genetics and support from in vivo models is limited. This ViCTER brings together investigators with the necessary expertise to study joint effects of genes and the environment in both mouse and human studies to address critical data gaps. In this proposal we leverage resources of the Early Autism Risk Longitudinal Investigation (EARLI) and the mouse exposure paradigm developed as part of the University of Southern California Children's Environmental Health Center (SC-CEHC) to integrate findings from animal and human data addressing susceptibility to prenatal air pollution exposure for ASD. The ViCTER seeks to accomplish this through the following three projects: (1) to investigate the effect of prenatal near-roadway nano-scale particles (nPM) exposure on mouse behavior and on transcription in mouse brain and mouse peripheral blood; (2) to explore if prenatal NRAP and PM2.5 exposure are associated with differential epigenetic and transcription profiles in cord blood from EARLI, and if these profiles are associated with ASD; and (3) to expand the investigation of prenatal NRAP and PM2.5 effects on ASD in EARLI to incorporate genetic susceptibility. Taken together, findings from this consortium have the potential to rapidly influence our knowledge of gene-environment interaction and provide a structure for future integrative studies that would not be possible without development of this collaborative framework.

 描述（由应用程序提供）：该提案旨在建立一个虚拟联盟，用于翻译/跨学科环境研究（Victer），以建立研究性专业知识，以研究自闭症谱系障碍（ASD）基于的建立空气污染协会（ASD）的机制，尽管是免费的小鼠和流行病学研究。我们建立在第一个预期R01（R01 ES023780）的基础上，评估了产前空气污染物暴露，认知定义和ASD之间的关系。我们的团队和其他人此前曾报告说，基于居住在高速公路附近的生活，靠近道路空气污染（NRAP）以及在妊娠期间直径小于2.5微米（PM2.5）的水平增加的ASD风险增加。但是，很少有研究检查了环境和遗传学的关节作用以及体内模型的支持是有限的。 Victer将研究人员汇集了必要的专业知识，以研究小鼠和人类研究中基因和环境的关节影响，以解决关键的数据差距。在这项建议中，我们利用早期自闭症风险纵向调查（Earli）和小鼠暴露范式作为南加州大学儿童环境健康中心（SC-CEHC）开发的小鼠暴露范式，以整合来自动物和人类数据的发现，以解决对ASD的产前空气污染暴露的易感性。 Victer试图通过以下三个项目来实现这一目标：（1）研究近​​路近路纳米级颗粒（NPM）对小鼠行为以及小鼠脑和小鼠外周血中转录的影响； （2）探索产前NRAP和PM2.5是否与Earli的脐带血的差异表观遗传和转录谱有关，以及这些特征是否与ASD相关； （3）扩大产前NRAP和PM2.5对ASD的影响的投资，以融合遗传易感性。综上所述，该财团的发现有可能快速影响我们对基因环境相互作用的了解，并为未来的综合研究提供结构，而没有这种协作框架的发展，这是不可能的。