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

 描述（由申请人提供）：该提案旨在建立一个转化/跨学科环境研究虚拟联盟（ViCTER），以建立调查专业知识，通过免费的小鼠和流行病学研究来研究自闭症谱系障碍（ASD）的空气污染相关机制。我们建立在第一个前瞻性R 01（R 01 ES 023780）评估产前空气污染物暴露，认知缺陷和ASD之间的关系。我们的团队和其他人以前曾报告过ASD的风险增加，这是基于居住在高速公路附近，暴露于近道路空气污染（NRAP），以及妊娠期间直径小于2.5微米的颗粒物（PM2.5）水平增加。然而，很少有研究检查环境和遗传学的联合作用，并且来自体内模型的支持是有限的。该ViCTER汇集了具有必要专业知识的研究人员，以研究基因和环境在小鼠和人类研究中的联合作用，以解决关键的数据缺口。在这项提案中，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）的一部分开发的小鼠暴露范式，整合来自动物和人类数据的研究结果，解决ASD产前空气污染暴露的敏感性。ViCTER试图通过以下三个项目来实现这一目标：（1）研究产前近道路纳米尺度颗粒（nPM）暴露对小鼠行为以及小鼠大脑和小鼠外周血中转录的影响;（2）探索产前NRAP和PM2.5暴露是否与EARLI的脐带血中的差异表观遗传和转录谱相关，以及这些特征是否与ASD相关;以及（3）扩大产前NRAP和PM2.5对EARLI中ASD影响的研究，以纳入遗传易感性。总的来说，这个联盟的研究结果有可能迅速影响我们对基因-环境相互作用的认识，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.