Fetal Alcohol Exposure and Sudden Infant Death Syndrome

胎儿酒精暴露与婴儿猝死综合症

基本信息

批准号：
7274853
负责人：
ROBIN Lynn HAYNES
金额：
$ 11.87万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-08-10 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7274853
关键词：
A Mouse Address Adverse effects Affect Alcohol consumption Alcohols Anatomy Animal Model Animals Area Asphyxia Autonomic Dysfunction Binding Boston Brain Stem Cell Count Cell physiology Characteristics Child Clinical Cognitive Collaborations Communities Continuing Education Cultured Cells Data Development Emotional disorder Fetal Alcohol Exposure Fetal alcohol effects First Pregnancy Trimester Forebrain Development Goals Grant Homeostasis Hospitals Human Hypercapnia Hypoxia Infant Laboratories Learning Mediating Medical Medulla Oblongata Methods Modeling Molecular Biology Morbidity - disease rate Mus Neurologic Neurons Numbers Patients Pediatric Hospitals Perinatal Exposure Physiological Play Pregnancy Pregnant Women Principal Investigator Reporting Research Infrastructure Resources Risk Risk Factors Role Science Series Serotonin Signaling Molecule Sleep Sudden Death Sudden infant death syndrome System Techniques Testing Therapeutic Thinking United States Work Writing alcohol exposure base binge drinking critical developmental period density drinking in utero interest laboratory facility medullary serotonergic system migration mouse model neurobehavioral neurochemistry postnatal prenatal exposure problem drinker programs receptor receptor binding respiratory response serotonin receptor serotonin transporter stem stressor transcription factor

项目摘要

Our laboratory has provided evidence that a large proportion of infants dying of Sudden Infant Death Syndrome (SIDS) have abnormalities of the medullary serotonergic (5-HT) system, which is responsible for modulation of multiple homeostatic functions. A risk factor for SIDS is maternal alcohol consumption during the first trimester. We hypothesize that in utero exposure to alcohol during early gestation affects the development and function of the medullary 5-HT system. A mouse model of maternal alcohol consumption will be used to address the hypotheses that prenatal alcohol exposure affects the: (1) cellular and neurochemical development and functions of 5-HT neurons; (2) the development of 5-HT neurons through the suppression of 5-HT-specific transcription factor Pet-1 and the signaling molecules responsible for 5-HT precursor development; and (3) the chemoreception function of 5-HT neurons in response to hypercarbia and hypoxia. The overall goal of this project is to understand the basis of fetal alcohol exposure as a risk factor for SIDS, and to ultimately develop therapeutic strategies to alleviate the adverse effects associated with fetal alcohol exposure. The project will be done at Children's Hospital Boston with access to all resources from Children's, as well as surrounding hospitals in the Harvard community, including excellent laboratory facilities, seminar series, and continuing education. The project proposed will be done in close association with a program project on SIDS involving Harvard, Dartmouth, and Yale. This infrastructure will allow invaluable collaborations with experts who are co-sponsors of this project. Nearly all aspects of this project are new to the candidate, providing the opportunity to learn multiple new areas of science. Through the course of this work, the candidate will progress to independence, and prepare for writing an RO1. The RO1 will stem from work proposed in this grant, and thus, this work will be a critical step towards the establishment of a laboratory with the candidate as Principal Investigator.

我们的实验室提供了证据表明，死于猝死综合征（SIDS）的大部分婴儿具有髓质血清素能（5-HT）系统的异常，该系统负责调节多种稳态功能。小岛屿发展中国家的危险因素是头三个月的孕产妇饮酒。我们假设在早期妊娠期间的子宫暴露于酒精时会影响髓质5-HT系统的发育和功能。孕产妇饮酒的小鼠模型将用于解决产前酒精暴露会影响的假设：（1）5-HT神经元的细胞和神经化学发育和功能；（2）通过抑制5-HT特异性转录因子PET-1和负责5-HT前体发育的信号传导分子来发展5-HT神经元；（3）5-HT神经元的化学感受函数响应高碳酸盐和缺氧。该项目的总体目标是将胎儿酒精暴露的基础作为小岛屿发展中国家的危险因素，并最终制定治疗策略，以减轻与胎儿酒精暴露有关的不良影响。该项目将在波士顿儿童医院完成，并从哈佛大学社区中获得所有资源，包括出色的实验室设施，研讨会系列和继续教育。提出的项目将与有关哈佛，达特茅斯和耶鲁大学的小岛屿发展中国家的计划项目密切关联。这种基础架构将允许与该项目共同发起人的专家合作。几乎所有方面候选人是新的项目，提供了学习多个新科学领域的机会。在这项工作的过程中，候选人将晋升为独立性，并为编写RO1做准备。 RO1将源于本赠款中提出的工作，因此，这项工作将是朝着候选人担任首席研究人员建立实验室的关键一步。