The Ventral Medulla and the Sudden Infant Death Syndrome

腹延髓和婴儿猝死综合症

基本信息

批准号：
8607742
负责人：
Hannah Chase Kinney
金额：
$ 167.37万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-04-01 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8607742
关键词：
Address Affect Age Aminobutyric Acids Anatomy Animal Model Animals Arousal Autopsy Binding Biological Markers Biology Blood Blood Platelets Brain Brain Stem Brain region Candidate Disease Gene Cessation of life Chemicals Childhood Clinical Commit Country Databases Defect Development Discipline Disease Dorsal Drug Formulations Failure Family Family member Functional disorder Future Gene Expression Gene Expression Profile Genes Genome Hippocampus (Brain)Human Hypoxia Impairment Infant Infant Mortality Institution Investigation Laboratories Larynx Lasers Life Link Medical Medical Examiners Medulla Oblongata Methodology Microscopy Molecular Molecular Profiling Mus Neuroanatomy Neurobiology Neurons Neurotransmitters Nicotine Pathology Pathway interactions Pharmaceutical Preparations Physiological Play Principal Investigator Prosencephalon Recording of previous events Research Research Personnel Risk Role Sampling Series Serotonin Serum Signal Transduction Signaling Protein Site Sleep Sudden infant death syndrome System Techniques Technology Tissues United States Ursidae Family base brain tissue case control comparative critical developmental period design experience gamma-Aminobutyric Acid infant animal innovation nano-string neurochemistry neuropathology neurotransmission novel postnatal prenatal exposure prevent programs public health relevance relating to nervous system response stressor synaptic function tissue resource tool transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): The sudden infant death syndrome (SIDS) is the sudden death of an infant that remains unexplained after a complete review of the history, autopsy, and death scene investigation; it is the leading cause of postneonatal infant mortality in the United States today. Based upon our findings to date, we hypothesize that SIDS is due to an underlying abnormality in the medullary homeostatic network that: 1) results in a failure of protective responses to life-threatening stressors during sleep in a critical developmental period; and 2) importantly involves serotonin (5-hydroxytryptamine, 5-HT), y-aminobutyric acid (GABA), and their potential interactions with other neurotransmitter systems and the signal transduction family 14-3-3. Initiated in 1998, our program brings together a highly committed group of 23 investigators and their trainees to address the potential role of the brain in SIDS. Located at 3 medical institutions across the country and the medical examiner's system in San Diego, CA, we bring to bear upon the SIDS problem outstanding expertise in multiple clinical and scientific disciplines in 3 integrated projects and 2 cores (Administrativ and Neuroanatomy). The 7 inter-related themes proposed for investigation with state-of-the-art methodologies in the next (fourth) cycle are: 1) gene expression profiles of the medullary homeostatic network in SIDS infants and animal models (Projects I and II; 2) the interaction of prenatal exposures (hypoxia and nicotine) with preexisting 5-HT dysfunction that potentially leads to homeostatic impairment in the postnatal period (Projects II and III); 3) the mechanism(s) of physiological derangements in protective homeostatic responses related to 5-HT and GABA, including autoresuscitation, arousal, and the laryngeal chemoreflex (Projects II and III); 4) the development and connectivity of subtypes of brainstem 5-HT neurons related to different homeostatic functions (Projects III); 5) a potential link between abnormalities in the caudal/rostral 5-HT domains of the brainstem and hippocampal targets in SIDS brains (Project I); 6) treatment of abnormalities in animal models with specific drugs (Project II); and 7) the development of future biomarkers of brainstem pathology in SIDS infants.

描述（由申请人提供）：突然的婴儿死亡综合征（SIDS）是婴儿的突然死亡，在对历史，尸检和死亡现场调查进行完整的审查后，仍无法解释；这是杀害后婴儿死亡率的主要原因今天的美国。根据我们迄今为止的发现，我们假设SIDS是由于髓质体内稳态网络中的潜在异常引起的：1）导致在关键发育期间睡眠期间对危及生命的压力源的保护性反应；和2）重要的是涉及5-羟色胺（5-羟基丙胺，5-HT），Y-氨基丁酸（GABA）及其与其他神经递质系统和信号转导家族的潜在相互作用14-3-3。我们的计划成立于1998年，汇集了一个由23位调查人员及其受训者组成的备受推崇的小组，以解决大脑在SIDS中的潜在作用。我们位于全国的3个医疗机构和加利福尼亚州圣地亚哥的体检医师系统中在三个综合项目和2个核心的多个临床和科学学科中（行政管理和神经解剖学）。下一个（第四）周期中提议调查的7个相互相关主题是：1）在SIDS婴儿和动物模型（项目I和II; 2）中，髓样稳态网络的基因表达特征（项目； 2）相互作用（低氧和尼古丁）与潜在的5-螺旋式效果的相互作用，以置于预先启动的次数。（II和III项目）； 3）与5-HT和GABA有关的保护性稳态反应中生理危险的机制，包括自动震荡，唤醒和喉部Chemoreflex（项目II和III）； 4）与不同稳态功能有关的脑干5-HT神经元子类型的发展和连通性（项目III）； 5）脑干的尾/鼻尾5-HT结构域中的异常与SIDS大脑中的海马靶标之间的潜在联系（项目I）； 6）用特定药物的动物模型治疗异常（项目II）； 7）在SIDS婴儿中，未来的脑干病理生物标志物的发展。