Lipidomics of meconium in neurodevelopment

 描述(申请人提供)：脂类对健康的神经发育至关重要，在大脑的不同区域都有不同程度的丰富，是人体新陈代谢不可或缺的部分。胎粪是新生儿第一次排便，大约在怀孕12周时开始积累，含有较高的脂肪含量。因此，胎粪可能为了解自闭症谱系障碍的早期病因学中出现的神经发育异常提供了一个窗口。这项建议将量化和比较自闭症谱系障碍早期事件的前瞻性丰富风险队列中典型发育迟缓儿童和神经发育迟缓儿童胎粪中的脂质含量。为了扩大假定识别的脂质生物标志物的相关性，将阐明生物标志物的结构，并将来自队列的样本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粪便进行比较。最后，将在合适的基质中开发有针对性的方法，用于未来对生物标记物的验证。我们将在以下三个具体目标中进行这项研究：目标1.在预期的强化风险队列中，确定ASD和对照之间具有不同丰度的未知层析特征。目的2.从结构上阐明ASD的可能生物标志物，并比较胎粪、胎盘和脐带血中的脂质含量。目的3.建立和验证ASD可能生物标志物的靶向定量方法。

 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.