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（由申请人提供）：候选人是一名分子流行病学家，主要研究产前/生命早期接触环境和社会污染物影响儿童健康的编程机制，特别关注神经发育与环境相关的研究。空气污染和神经发育不良，该提案的目标是通过识别新的线粒体（mt）生物标志物，通过识别新的线粒体（mt）生物标志物，增加日益增长的将城市空气污染物、压力和神经发育不良联系起来的研究，通过这些生物标志物，可以在子宫内暴露于空气污染和神经发育不良之间。通过 Rosalind Wright 博士、Andrea Baccarelli、Robert Wright、Michelle Bosquet Enlow、Avraham Reichenberg、Luca Lambertini 和 Liming Lang 博士的正式课程和专家指导，该奖项将使我能够发展所需的知识和技能。成为一名独立的跨学科环境健康科学家并实现我的长期职业目标：建立一个有竞争力且成功资助的项目来研究环境暴露（例如空气污染/压力）对人体的累积影响虽然该奖项侧重于神经行为结果，但值得注意的是，鉴于大量具有 mt 基础的儿童疾病，所获得的知识和技能将广泛适用于一系列儿童健康结果。（例如哮喘、肥胖、自闭症和注意力障碍）。具体来说，候选人将 1) 在 Baccarelli 博士和 Lambertini 的实验室接受广泛的实验室培训，以进一步提高我的分子技能；测量和解释相互作用的社会压力源的培训；3）接受涉及选择、管理和解释整个幼儿期神经发育评估的指导和实践培训。、胎盘和脐带血）关于产前环境暴露（例如城市空气污染物和压力）和早期神经行为表型的目的是使用最先进的线粒体 DNA 分析。通过在母胎界面（例如胎盘和脐带血）测量的一组氧化损伤、异质性和 mtDNA 丰度的互补标记来确定损伤。这些标记具有使其非常适合生物标记开发的特性。：1）已被证明会因高度环境暴露而改变；2）可以标记受损线粒体的存在，这是大脑特别容易受到影响的全身氧化应激的主要来源。我们将利用资源现有的表型良好的城市和种族混合妊娠队列[代际压力机制（PRISM）研究的编程]与现有的生物样本以及神经行为和环境数据。