Developmental Exposure Alcohol Research Center

发育暴露酒精研究中心

• 批准号: 8137631
• 负责人: LINDA PATIA SPEAR
• 金额: $ 159.73万
• 依托单位: STATE UNIVERSITY OF NY,BINGHAMTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8137631
• 关键词: Developmental; Exposure; Alcohol; Research; Center

The developing nervous system is among the most vulnerable targets of ethanol. Unlike other organs, the brain develops over a protracted period. It is susceptible to ethanol toxicity from its inception (at gastrulation), through gestation, infancy, and adolescence. We will focus on the effects of ethanol exposure during the fetal/neonatal and adolescent periods because they are (1) times of critical and rapid brain growth and (2) when developing humans are most likely exposed to ethanol, i.e., times of prime clinical relevancy. Indeed, fetal and adolescent exposures are key risk factors for alcoholism in adults. In turn, adult alcoholics produce children with fetal alcohol spectrum disorder and adolescents predisposed to early initiation into alcohol use. This increases adolescents' susceptibility to developing alcohol use disorders, and hence perpetuates the cycle. This developmental programming constitutes what we have dubbed the "alcoholism generator." The binding themes of our Developmental Exposure Alcohol Research Center (DEARC) are (1) that ethanol affects neuroadaptation in the developing nervous system, (2) that ethanol-induced effects depend upon the developmental stage of the nervous system, and (3) common mechanisms by which brain development alters the effects of ethanol and conversely ethanol affects brain development. The themes of the DEARC bind the novel hypotheses raised in each project. Four highly integrated Main Projects will examine mechanisms of ethanol-related developmental defects. These projects are studies of the effects of developmental exposure to ethanol during the prenatal/infant or adolescent periods (1) on the fates of neural stem cells and dendritic plasticity, (2) on experience-induced plasticity in chemosensory function and development, (3) on ontogenetic programming and age-related mechanisms of positive and negative ethanol reinforcement, and (4) on the role of neurotransmitter systems in adolescent-typical ethanol sensitivities. Senior alcohol researchers and developmental neurobiologists will direct these projects. The grease and glue underpinning the synergistic interactions among these investigators comes from the Administrative Core and three scientific cores (Animal, Cell/Molecular Biology, and Neuroanatomy Cores). The center will continue to serve as an incubator for ideas, new projects, and the growth of investigators. One mechanism for these activities will be the Pilot Project Program. The proposed pilot projects will complement and extend the Main Projects. As a unit, the proposed center will meld the talents of senior biomedical and behavioral researchers at three campuses of the State University of New York: Binghamton University in Binghamton, SUNY-Cortland, and Upstate Medical University in Syracuse. Thus, the DEARC will serve as a nexus of alcohol research in Central New York and as a beacon for national activities.

发育中的神经系统是乙醇最脆弱的靶标之一。与其他器官不同，大脑在旷日持久的时期发展。它易受乙醇毒性的造成（胃肠道），妊娠，婴儿期和青春期的影响。我们将重点关注胎儿/新生儿和青少年期间乙醇暴露的影响，因为它们是（1）脑部临界和迅速生长的时间，并且（2）当发展人类很可能会暴露于乙醇时，即主要临床相关性。实际上，胎儿和青少年暴露是成人酒精中毒的关键风险因素。反过来，成人酒精中毒会产生胎儿酒精谱系障碍的儿童，青少年易于早期开始使用酒精。这增加了青少年对发展饮酒障碍的敏感性，因此使周期永存。这种发展节目构成了我们称之为“酒精中毒生成器”的产品。我们发育暴露酒精研究中心（DEARC）的结合主题是（1）乙醇会影响发育中神经系统中神经适应的神经适应，（2），乙醇诱导的作用取决于神经系统的发育阶段，（3）常见机制，通过这些机制可以改变乙醇和交流乙醇影响大脑发育的影响。 Dearc的主题结合了每个项目中提出的小说假设。四个高度集成的主要项目将检查与乙醇相关的发育缺陷的机制。这些项目是对产前/婴儿或青少年期（1）对神经干细胞和树突可塑性命运的发育暴露的影响，（2）对化学感应功能和发育中经验可塑性的影响（（3），（3）对非基础编程和阳性和阳性的乙醇和元素的阳性机制，以及（4）促进了（4）的促进剂和4）。青少年典型乙醇敏感性。高级酒精研究人员和发育神经生物学家将指导这些项目。这些研究者之间协同相互作用的基础的油脂和胶水来自行政核心和三个科学核心（动物，细胞/分子生物学和神经解剖核心）。该中心将继续作为思想，新项目和研究人员成长的孵化器。这些活动的一种机制将是试点项目计划。拟议的试点项目将补充并扩展主要项目。 作为一个单位，拟议的中心将在纽约州立大学的三个校园里融合了高级生物医学和行为研究人员的才能：宾夕法尼亚州宾夕法尼亚州宾汉顿大学的宾厄姆顿大学和锡拉丘兹的上州医科大学。因此，Dearc将在纽约中部充当酒精研究的联系，并成为国家活动的灯塔。