ALCOHOL AND BRAIN DEVELOPMENT

酒精与大脑发育

• 批准号: 6371360
• 负责人: JAMES R WEST
• 金额: $ 27万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-29 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6371360
• 关键词: alcoholic beverage consumption; avoidance behavior; blood tests; brain disorders; congenital oral /facial /cranial defect; developmental neurobiology; embryo /fetus toxicology; ethanol; fetal alcohol syndrome; gestational age; laboratory mouse; morphology; neurogenesis; olfactions

DESCRIPTION: (Adapted from the Investigator's Abstract) Although it has been 25 years since fetal alcohol syndrome (FAS) was first defined, it is still not clear whether or not the embryo suffers long-term brain deficits after alcohol exposure early in gestation. Since many women are binge drinkers, including those who can stop or significantly reduce their alcohol consumption once they are aware they are pregnant, and since many of them will not know they are pregnant for at least several weeks after conception, binge drinking during this early period may represent a very dangerous practice. Alarmingly, recent studies have provided evidence that contradicts the commonly held view that early pregnancy is not a vulnerable period for inducing birth defects. Therefore, until we understand the consequences of such exposure, misconceptions about the vulnerability of the conceptus during early development increases the likelihood of alcohol related birth defects, and delays the chances that the cause of those birth defects will be identified. This competitive renewal application represents the first comprehensive attempt to evaluate the effects of binge-like alcohol exposure during different discrete developmental events early in pregnancy on long-term structure and function of the brain. First, it utilizes the C57BL/6J mouse, which is known to be susceptible to alcohol-induced craniofacial and brain dysmorphology associated with FAS. Second, the timing of the alcohol exposure will focus on discrete embryonic events. Third by using a standard series of peak blood alcohol concentrations, it will be possible to compare the "relative vulnerability" of different early prenatal periods. The studies will determine whether embryos exposed to alcohol during early development, even at blood alcohol concentrations (BACs) below that resulting in facial dysmorphology, nevertheless display lasting central nervous system dysfunction. Specific Aim #1 will evaluate the effects of oral alcohol exposure occurring during gastrulation (gestation day [GD] 7:0) on fetal (GD14:0) somatic growth, brain morphology and craniofacial anomalies, to determine the threshold at which brain deficits may be induced in the absence of craniofacial dysmorphology. Specific Aim #2 will evaluate the effects of alcohol exposure during specific developmental events from fertilization to early gestation. Specific Aim #3 will test the hypothesis that binge-like alcohol exposure that is time-locked to specific developmental events early in development will have more deleterious effects than will similar duration of alcohol exposure that specifically misses the critical events identified in Specific Aim #2. The results will be beneficial for counseling women about the risks of drinking during the initial weeks of pregnancy, and may help to explain the variation in brain damage observed in children damaged by in utero alcohol exposure. The studies also will provide the foundation for mechanistic studies to identify how alcohol exposure damages the developing conceptus.

描述：(改编自《调查者摘要》)尽管已经25岁了 自从胎儿酒精综合征(FAS)被首次定义以来，它仍然没有被定义 弄清胚胎在酒精后是否会遭受长期的大脑缺陷 在怀孕早期暴露。由于许多女性都是酗酒者，包括 那些能够停止或显著减少饮酒的人，一旦他们 都知道自己怀孕了，因为她们中的许多人不会知道自己怀孕了 怀孕后至少怀孕几周，期间酗酒 这一早期阶段可能代表着一种非常危险的做法。令人担忧的是，最近 研究提供的证据与普遍持有的观点相矛盾 早期怀孕并不是导致出生缺陷的脆弱时期。 因此，在我们了解这种暴露的后果之前， 在早期对概念的脆弱性的误解 发育增加了与酒精相关的出生缺陷的可能性，并且 推迟了那些出生缺陷的原因被确定的机会。 这一竞争性续签申请是第一次全面尝试 评估暴饮式酒精暴露在不同时期的影响 妊娠早期离散发育事件对长期结构的影响 大脑的功能。首先，它利用了C57BL/6J小鼠，这是已知的 易患酒精引起的头面部和脑畸形 与Fas有关。其次，接触酒精的时间将集中在 离散的胚胎事件。第三，使用一系列标准的峰值血液 酒精浓度，将有可能比较“相对的 不同早期胎儿期的易损性。研究将确定 胚胎在发育早期是否接触酒精，甚至在血液中也是如此 酒精浓度(BAC)低于此水平会导致面部畸形， 但表现为持久的中枢神经系统功能障碍。特定目标 #1将评估口服酒精暴露的影响 原肠发育(妊娠期[GD]7：0)对胎儿(GD14：0)体细胞生长、脑发育的影响 形态和颅面异常，以确定阈值 在没有颅面畸形的情况下，可能会导致脑功能障碍。 特定目标2将评估酒精暴露在特定时间段的影响 从受精到早孕的发育事件。具体目标#3 将检验一种假设，即时间锁定的狂欢类酒精暴露 对发育早期的特定发育事件会有更多 有害的影响会比类似的酒精暴露时间长 特别遗漏了具体目标2中确定的关键事件。 研究结果将有助于对女性进行饮酒风险的咨询。 在怀孕的最初几周，这可能有助于解释 宫内酒精暴露对受损儿童脑损伤的观察。这个 研究还将为机械研究提供基础，以确定 酒精暴露如何损害发育中的胚胎。