Lipidomics of meconium in neurodevelopment

胎便在神经发育中的脂质组学

• 批准号: 9090727
• 负责人: Nathaniel W. Snyder
• 金额: $ 23.48万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-22 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9090727
• 关键词: Address; Androgens; Autistic Disorder; Behavior; Biological Markers; Blood; Brain; Brain region; Carbon; Chemical Structure; Chemicals; Child; Child health care; Clinical assessments; Cohort Studies; Communication; Complex; DNA Methylation; Defecation; Defect; Development; Elderly; Ensure; Environment; Epigenetic Process; Etiology; Event; Feces; Folic Acid; Future; General Population; Goals; Head; Health; Human; Infant; Infection; Inflammatory Response; Institutes; Investigation; Knowledge; Laboratories; Light; Lipids; Meconium; Mediator of activation protein; Metabolism; Methods; Modification; Molecular Genetics; Morphologic artifacts; Neurodevelopmental Disorder; Newborn Infant; Outcome; Oxidative Stress; Placenta; Positioning Attribute; Pregnancy; Prevalence; Research; Resolution; Resources; Risk; Risk Factors; Sampling; Science; Social Interaction; Source; Spottings; Steroids; Structure; Technology; Testing; Time; Umbilical Cord Blood; Unsaturated Fats; Validation; Work; analytical method; autism spectrum disorder; base; biomarker panel; cohort; developmental disease; disease classification; disorder control; disorder risk; experience; feeding; fetal; histone methylation; in utero; instrument; interest; liquid chromatography mass spectrometry; male; maternal serum; method development; methyl group; neurodevelopment; oxidized lipid; prenatal; prenatal influence; prospective; public health relevance; repetitive behavior; research study; trait

 DESCRIPTION (provided by applicant): Lipids are critical to healthy neurodevelopment, are variably enriched across regions of the brain, and are integral to human metabolism. Meconium, the first bowel movements of a newborn, begin accumulation in approximately the 12th week of gestation, and contains high lipid content. Thus, meconium may provide a window into the abnormal neurodevelopment that occurs in the early etiology of autism spectrum disorder. This proposal will quantify and compare the lipid content of meconium in typically developing versus neurodevelopmentally delayed children from a prospective enriched risk cohort of early events in autism spectrum disorder. To extend the relevance of the putatively identified lipid biomarkers, the structures of the biomarkers will be elucidated, and the lipid content of the samples derived from the cohort will be compared to meconium from healthy newborns as well as other biospecimens from newborns. Finally, targeted methods will be developed in suitable matrices for future validation of the biomarkers. We will conduct this research in three specific aims as follows; Aim 1. Identify unknown chromatographic features with differential abundance between ASD and controls in a prospective enriched risk cohort. Aim 2. Structurally elucidate the putative biomarkers of ASD and compare the lipid content of meconium, placenta, and cord blood. Aim 3. Develop and validate a targeted method for the quantitation of putative biomarkers of ASD.

 描述（由申请人提供）：脂质对健康的神经发育至关重要，在大脑的各个区域富集，并且是人体代谢的组成部分。胎粪是新生儿的第一次排便，大约在妊娠第12周开始开始积累，并含有高脂质含量。因此，胎粪可能提供了一个窗口，在自闭症谱系障碍的早期病因发生的异常神经发育。这项建议将量化和比较胎粪中的脂质含量在典型的发展与神经发育迟缓的儿童从一个前瞻性的丰富的风险队列的早期事件自闭症谱系障碍。为了扩展脓毒症鉴定的脂质生物标志物的相关性，将阐明生物标志物的结构，并将来自队列的样品的脂质含量与来自健康新生儿的胎粪以及来自新生儿的其他生物标本进行比较。最后，将在合适的基质中开发有针对性的方法，用于未来生物标志物的验证。我们将在以下三个具体目标进行这项研究：目标1。在前瞻性富集风险队列中识别ASD和对照之间丰度差异的未知色谱特征。目标2.从结构上阐明ASD的假定生物标志物，并比较胎粪、胎盘和脐带血的脂质含量。目标3.开发并验证用于定量ASD推定生物标志物的靶向方法。