BIOMARKERS OF NEUROTOXICITY ASSOCIATED WITH FETAL TOBACCO SMOKE EXPOSURE?

与胎儿烟草烟雾暴露相关的神经毒性生物标志物？

• 批准号: 8167657
• 负责人: Rachel Elizabeth Neal
• 金额: $ 15.11万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167657
• 关键词: Adult; Affect; Alcohol consumption; Arachidonic Acids; Aromatic Hydrocarbons; Arsenic; Behavioral; Biological Markers; Carbon Monoxide; Chemicals; Choline; Cigarette; Computer Retrieval of Information on Scientific Projects Database; Cotinine; Decidual Cell Reactions; Developmental Delay Disorders; Disease model; Embryo Resorption; Environment; Ethanol; Exposure to; Fetal Alcohol Spectrum Disorder; Fetal Growth; Fetal Growth Retardation; Fish Oils; Funding; Grant; Homeostasis; Hydrogen Cyanide; Institution; Lipids; Live Birth; Low Birth Weight Infant; Mediating; Mediator of activation protein; Metabolism; Microcephaly; Microphthalmos; Neurocognitive; Nicotine; Nutrient; Omega-3 Fatty Acids; Peripheral; Phospholipids; Placentation; Reporting; Research; Research Personnel; Resources; Rodent Model; Serum Markers; Smoker; Source; Supplementation; Tissues; Tobacco smoke; Toxic effect; United States National Institutes of Health; Withdrawal; alcohol exposure; cigarette smoking; craniofacial; fetal; implantation; malformation; neurotoxicity; protein metabolite

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Approximately 45 million U.S adults are active smokers. Cigarette smoke consists of more than 4000 chemical compounds including polycylic aromatic hydrocarbons, carbon monoxide, hydrogen cyanide, and arsenic. Nicotine, the primary addictive component of cigarettes, is rapidly metabolized to cotinine with a systemic clearance by day 3 post-withdrawal. Biomarkers of cigarette smoke exposure which are present post-nicotine clearance, and which are peripheral markers of sustained neurotoxicity, are lacking. The emphasis of the first study (April-December 2009) was upon identification of abnormalities in tissue protein and metabolite homeostasis which are mirrored by serum markers of toxicity. In the current proposal (Jan-March 2010), we are establishing whether alcohol exposure induced IUGR is mediated by uterine/placental phosphatide availability. Fetal Alcohol Spectrum Disorders (FASD) affect approximately 1 per 100 live births of which low birth weight (LBW) and developmental delays are most common. In rodent models of FASD, gestational exposure to ethanol induces increased embryo resorption and intrauterine growth restriction (IUGR); persistent neurocognitive and behavioral deficits; as well as a variety of craniofacial malformations including microphthalmia and microcephaly . In FASD models, supplementation with phosphatide precursors [choline or omega-3 long-chain polyunsaturated fatty acids (omega-3 LC-PUFAs; fish oil supplement)] during decidualization/placentation alleviates IUGR. Arachidonic acid availabilityan established mediator of successful implantation, decidualization, and fetal growth--is mediated by phosphatide transport/metabolism. In the coming year, we will probe whether maternal alcohol consumption modifies the uterine/placental lipid environment leading to IUGR and LBW. Further we will examine whether maternal nutrient supplementation with LC-PUFAs or choline, which is reported to alleviate LBW, will modify the uterine/placental lipid profiles.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 大约4500万美国成年人是活跃的吸烟者。香烟烟雾由4000多种化合物组成，包括多环芳烃、一氧化碳、氰化氢和砷。尼古丁是香烟的主要成瘾成分，在戒烟后第3天，尼古丁会迅速代谢为可替宁，并被全身清除。香烟烟雾暴露的生物标记物是尼古丁清除后存在的，是持续神经毒性的外围标记物，缺乏。第一项研究(2009年4月至12月)的重点是确定血清毒性标记物所反映的组织蛋白和代谢物稳态的异常。 在目前的提案中(2010年1月至3月)，我们正在确定酒精暴露是否通过子宫/胎盘磷脂的可获得性来调节宫内发育迟缓。胎儿酒精谱障碍(FASD)影响大约每100个活产儿中的1个，其中低出生体重(LBW)和发育迟缓最为常见。在FASD的啮齿动物模型中，孕期接触乙醇会导致胚胎吸收增加和宫内生长受限(IUGR)；持续的神经认知和行为缺陷；以及各种颅面畸形，包括小眼球和小头畸形。在FASD模型中，在蜕膜化/胎盘形成期间补充磷脂前体[胆碱或omega-3长链多不饱和脂肪酸(omega-3 LC-PUFAs；鱼油补充)]可缓解IUGR。花生四烯酸的可获得性是成功着床、蜕膜形成和胎儿生长的中介物质--由磷脂运输/代谢调节。在接下来的一年里，我们将探讨母亲饮酒是否改变了导致IUGR和LBW的子宫/胎盘脂质环境。进一步，我们将检查孕妇补充LC-PUFAs或胆碱(据报道可减轻LBW)是否会改变子宫/胎盘的脂质状况。