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

 描述(由申请人提供)：这项建议寻求建立一个虚拟的转化性/跨学科环境研究联盟(VICTER)，以建立调查专业知识，通过免费的小鼠和流行病学研究，研究自闭症谱系障碍(ASD)已建立的空气污染协会背后的机制。我们建立在第一个前瞻性R01(R01 ES023780)的基础上，评估产前空气污染物暴露、认知缺陷和自闭症之间的关系。我们的团队和其他人之前曾报告说，居住在高速公路附近、暴露在路边空气污染(NRAP)中以及在怀孕期间暴露于直径小于2.5微米的颗粒物(PM2.5)水平会增加患自闭症的风险。然而，很少有研究考察环境和遗传学的联合影响，来自体内模型的支持也是有限的。这个Victer将拥有必要专业知识的研究人员聚集在一起，在老鼠和人类研究中研究基因和环境的联合影响，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)的资源和作为南加州大学儿童环境健康中心(SC-CEHC)一部分开发的老鼠暴露范例来整合动物和人类数据的结果，以解决ASD对产前空气污染暴露的易感性。Victer试图通过下列三个项目实现这一目标：(1)研究产前暴露于近道路纳米颗粒(NPM)对小鼠行为以及小鼠脑和小鼠外周血中转录的影响；(2)探讨产前暴露于NRAP和PM2.5是否与EARLI脐带血的表观遗传学和转录谱差异有关，以及这些图谱是否与ASD有关；以及(3)扩大对产前NRAP和PM2.5对EARLI中ASD影响的调查，以纳入遗传易感性。综上所述，该联盟的发现有可能迅速影响我们对基因-环境相互作用的知识，并为未来的综合研究提供一个结构，如果没有这个合作框架的发展，这是不可能的。

 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.