Mitochondrial Markers of Pollution, Stress, and Neurobehavior

污染、压力和神经行为的线粒体标记

基本信息

批准号：
8889788
负责人：
Kelly J Brunst
金额：
$ 11.38万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-20 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8889788
关键词：
Accounting Address Adenosine Affect Age-Months Air Pollutants Air Pollution Animals Arts Asthma Attention Autistic Disorder Award Behavior Behavioral Biochemical Biological Biological Markers Blood Brain Breathing Caliber Carbon Black Cell physiology Child Child health care Childhood Chronic Cognition DNA Damage DNA copy number Data Development Disease Encephalitis Environmental Exposure Environmental Health Epidemiologic Studies Epidemiologist Equilibrium Event Exhibits Exposure to Funding Future Goals Human Infant Infant Behavior Inflammation Knowledge Laboratories Leukocytes Life Limes Link Literature Maternal-Fetal Exchange Measures Mediating Mediation Memory Mentorship Mitochondria Mitochondrial DNA Modeling Molecular Mothers Mutation Neuraxis Obesity Outcome Oxidative Stress Oxidative Stress Induction Particulate Matter Pathology Pathway interactions Perinatal Exposure Phenotype Placenta Play Pollution Pregnancy Property Psychological Stress Rattus Reactive Oxygen Species Research Resources Respiratory System Respiratory tract structure Risk Role Scientist Seasons Site Social Interaction Source Stream Stress Testing Time Tissues Toxic effect Training Trauma Ultrafine Umbilical Cord Blood Umbilical cord structure ambient air pollution behavioral outcome career cohort cost effective design early childhood early life exposure executive function experience fetal frontal lobe improved in utero interest intergenerational maternal stress mitochondrial dysfunction neurobehavior neurobehavioral neurodevelopment novel oxidation oxidative damage particle pollutant prenatal prenatal environmental exposure programs public health relevance skills social social stress stressor traffic-related air pollution tripolyphosphate

项目摘要

DESCRIPTION (provided by applicant): The candidate is a molecular epidemiologist with primary research interest in the programming mechanisms by which prenatal/early-life exposure to environmental and social pollutants influences the health of children, with particular interest n neurodevelopment. With research linking ambient air pollution and poor neurodevelopment, the goal of this proposal is to add to the growing research linking urban air pollutants, stress and poor neurodevelopment by identifying novel mitochondrial (mt) biomarkers through which in utero exposures may be operating to impact future neurodevelopment. Through formal coursework and expert mentorship by Drs. Rosalind Wright, Andrea Baccarelli, Robert Wright, Michelle Bosquet Enlow, Avraham Reichenberg, Luca Lambertini and Liming Lang, this award will enable me to develop the knowledge and skills necessary to become an independent transdisciplinary environmental health scientist and achieve my long-term career goals: to establish a competitive and successfully funded program to study the cumulative effects of environmental exposures (e.g., air pollution/ stress) on the programming of biological mechanisms related to chronic childhood conditions. While this award focuses on neurobehavioral outcomes, it is worth noting that the knowledge and skills obtained will be broadly applicable to a range of child health outcomes given the large number of childhood conditions with mt underpinnings (e.g., asthma, obesity, autism, and attention disorders). Specifically, the candidate will 1) undergo extensive laboratory training in Drs. Baccarelli's and Lambertini's laboratories to further enhance my molecular skills; 2) obtain training in measuring and interpreting interactions involving social stressors; and 3) receive guidance and hands-on training in selecting, administering and interpreting neurodevelopmental assessments across early childhood. The proposed study will be the first to investigate complementary mtDNA biomarkers in two target tissues (e.g., placenta and cord blood) with respect to prenatal environmental exposures (e.g., urban air pollutants and stress) and early neurobehavioral phenotypes. The intent is to use state-of-art analyses of mtDNA damage by means of a panel of complementary markers of oxidative damage, heteroplasmy, and mtDNA abundance measured at the maternal-fetal interface (e.g., placenta and cord blood). These markers have properties that make them exceptionally well suited to biomarker development, as they: 1) have been shown to be altered by the environmental exposures; and 2) can mark the presence of damaged mitochondria, a primary source of systemic oxidative stress to which the brain is particularly vulnerable. This study is also highly cost effective as we will leverage the resources of an existing well-phenotyped urban and ethnically-mixed pregnancy cohort [PRogramming of Intergenerational Stress Mechanisms (PRISM) study] with existing biospecimens and neurobehavioral & environmental data.

描述（由适用提供）：候选人是一名分子流行病学家，具有对编程机制的主要研究兴趣，产前/早期生命暴露于环境和社会污染物会影响儿童健康，并特别感兴趣地神经发育。通过将环境空气污染和神经发育不良的研究联系起来，该提案的目的是通过鉴定新的线粒体（MT）生物标志物来增加与城市空气污染物，压力和不良神经发育联系的不断增长的研究，而在子宫内暴露在子宫内可能会影响未来的神经发育。通过DRS的正式课程和专家心态。 Rosalind Wright，Andrea Baccarelli，Robert Wright，Michelle Bosquet Enlow，Avraham Reichenberg，Luca Lambertini和Liming Lang，该奖项将使我能够发展出所必需的知识和技能，以成为独立的跨学科环境健康科学家并实现我的长期事业的独立性和成功的效果：为环境发展效果，以建立一个富有依风的计划（以稳健的效果，以实现屈从于屈从于努力，以实现累积的效果。污染/压力）关于与慢性儿童条件相关的生物学机制编程。尽管该奖项的重点是神经行为的结果，但值得注意的是，鉴于大量具有MT基础的儿童状况（例如，哮喘，肥胖症，自闭症和注意力障碍），获得的知识和技能将广泛适用于一系列儿童健康结果。具体来说，候选人将在DRS中接受广泛的实验室培训。 Baccarelli和Lambertini的实验室，以进一步提高我的分子技能； 2）在衡量和解释涉及社会压力源的相互作用方面获得培训； 3）在幼儿期选择，管理和解释神经发育评估方面接受指导和动手培训。拟议的研究将是第一个在两个目标时机（例如胎盘和脐带血）中研究完整的MTDNA生物标志物，就产前环境暴露（例如，城市空气污染物和压力）和早期神经行为的表型。目的是通过在母体 - 狂热界面（例如胎盘和脐带血）测得的氧化损伤，异质和mtDNA抽象的互补标记来使用MTDNA损伤的最新分析。这些标记具有使它们非常适合生物标志物发展的特性，因为它们：1）已证明环境暴露会改变； 2）可以标志着线粒体受损的存在，这是大脑特别脆弱的全身氧化应激的主要来源。这项研究也很有成本效益，因为我们将利用资源现有的现有的城市和伦理混合妊娠队列[代际压力机制的编程（PRISM）研究]与现有的生物测量和神经行为和环境数据。