ALCOHOL AND BRAIN DEVELOPMENT

酒精与大脑发育

• 批准号: 6509213
• 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/6509213
• 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：（根据研究者的摘要改编），尽管已经25 距胎儿酒精综合征（FAS）的数年才定义，它仍然不是 清除酒精后胚胎是否会遭受长期大脑缺陷 妊娠早期暴露。由于许多女性是暴饮暴食者，包括 那些可以停止或大量减少饮酒的人 知道他们怀孕了，因为许多人都不知道他们是 受孕后至少怀孕至少几周，在 这个早期可能代表了一种非常危险的做法。令人震惊的是，最近 研究提供了证据，表明通常认为的观点是 早期怀孕并不是诱发先天缺陷的脆弱时期。 因此，直到我们了解这种暴露的后果， 对早期概念的脆弱性的误解 发展增加了与酒精相关的先天缺陷的可能性，并且 延迟将发现这些出生缺陷的原因的机会。 此竞争性更新应用程序代表了首次全面尝试 评估在不同的情况下暴饮暴食的影响 怀孕初期的离散发展事件，以长期结构和 大脑的功能。首先，它利用C57BL/6J鼠标，已知 容易受到酒精引起的颅面和脑畸形学 与FAS相关。其次，酒精暴露的时机将重点放在 离散的胚胎事件。第三，使用一系列标准的峰血 酒精浓度，可以比较“相对 不同产前时期的脆弱性”。研究将决定 胚胎是否在早期发育中暴露于酒精，即使在血液中 酒精浓度（BAC）以下导致面部畸形， 然而，显示持久的中枢神经系统功能障碍。具体目标 ＃1将评估口服酒精暴露的影响 胎儿（GD14：0）的胃胃（妊娠日[GD] 7：0）体细胞生长，大脑 形态学和颅面异常，以确定阈值 在没有颅面畸形的情况下，可能会诱发脑缺陷。 特定目标＃2将评估特定期间酒精暴露的影响 从施肥到早期妊娠的发展事件。特定目标＃3 将检验以下假设，即狂暴的酒精暴露是滞留的 在开发初期进行特定的发展事件将有更多 有害影响比将持续的酒精暴露持续时间 特别错过了特定目标2中确定的关键事件。这 结果将对妇女咨询饮酒风险有益 在怀孕的最初几周内，可能有助于解释 在子宫酒精暴露中受损的儿童中观察到的脑损伤。这 研究还将为机械研究提供基础 酒精暴露如何损害发展中的概念。