Fetal Alcohol Exposure and Sudden Infant Death Syndrome

胎儿酒精暴露与婴儿猝死综合症

• 批准号: 6984253
• 负责人: ROBIN Lynn HAYNES
• 金额: $ 11.51万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 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/6984253
• 关键词: alcoholism /alcohol abuse; biological signal transduction; chemoreceptors; disease /disorder model; disease /disorder proneness /risk; embryo /fetus toxicology; fetal alcohol syndrome; hypercapnia; hypoxia; maternal behavior; model design /development; neurochemistry; protein localization; serotonin; serotonin receptor; serotonin transporter; sudden infant death syndrome; tissue /cell culture; transcription factor; western blottings

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.

我们的实验室提供的证据表明，很大一部分死于婴儿猝死综合征（SIDS）的婴儿有髓质5-羟色胺能（5-HT）系统的异常，该系统负责调节多种体内平衡功能。小岛屿发展中国家的一个危险因素是产妇在妊娠早期饮酒。我们假设在妊娠早期子宫内暴露于酒精会影响髓质5-羟色胺系统的发育和功能。母亲饮酒的小鼠模型将用于解决产前酒精暴露影响的假设：(1)细胞和神经化学发育和5-HT神经元的功能；(2)通过抑制5-HT特异性转录因子Pet-1和负责5-HT前体发育的信号分子来促进5-HT神经元的发育；(3) 5-HT神经元对高碳反应的化学接受功能