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：（改编自研究者摘要）虽然已经25年了， 自胎儿酒精综合征（FAS）首次被定义以来， 明确胚胎在酒精后是否会遭受长期的大脑缺陷 妊娠早期接触。由于许多女性都是酗酒者，包括 那些可以停止或显着减少他们的酒精消费，一旦他们 他们知道自己怀孕了，因为他们中的许多人不知道自己怀孕了。 怀孕后至少几周，在怀孕期间狂饮 这一早期阶段可能是一种非常危险的做法。令人震惊的是，最近 研究提供的证据与普遍持有的观点相矛盾， 怀孕初期并不是诱发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， 对孕体早期脆弱性的误解 发育增加了与酒精有关的出生缺陷的可能性， 延迟了这些出生缺陷的原因被发现的机会。 此次竞争性续期申请代表了首次全面尝试 为了评估在不同的时间段内酗酒的影响， 妊娠早期的离散发育事件对长期结构的影响， 大脑的功能。首先，它使用C57 BL/6 J鼠标，众所周知， 易受酒精诱导的颅面和脑畸形的影响 与FAS有关。第二，酒精暴露的时间将集中在 离散的胚胎事件第三，通过使用标准系列峰值血液 酒精浓度，将有可能比较“相对 不同的早期产前阶段的脆弱性“。这些研究将决定 胚胎在早期发育过程中是否暴露于酒精，即使在血液中， 酒精浓度（BAC）低于导致面部畸形的浓度， 但仍表现出持久的中枢神经系统功能障碍。具体目标 #1将评估在治疗期间发生的口服酒精暴露的影响。 原肠胚形成（妊娠日[GD] 7：0）对胎仔（GD 14：0）躯体生长、脑 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诱发脑缺陷。 具体目标#2将评估特定期间酒精暴露的影响 从受精到妊娠早期的发育事件。具体目标#3 将检验一个假设，即暴饮暴食式的酒精暴露是有时间限制的， 在发育早期的特定发育事件中， 有害的影响比类似的酒精暴露时间， 特别是错过了具体目标#2中确定的关键事件。的 研究结果将有助于向妇女提供有关饮酒风险的咨询。 在怀孕的最初几周，这可能有助于解释 在子宫内酒精暴露的儿童中观察到的脑损伤。的 研究还将为机制研究提供基础， 酒精暴露如何损害发育中的孕体