Developmental Exposure Alcohol Research Center

描述（由申请人提供）：发育中的神经系统是乙醇最易受伤害的目标之一。与其他器官不同，大脑的发育需要很长时间。它从一开始（原肠胚形成时）到妊娠期、婴儿期和青春期都易受乙醇毒性影响。我们将重点关注胎儿/新生儿和青少年时期乙醇暴露的影响，因为它们是（1）关键和快速大脑生长的时间，（2）发育中的人类最有可能暴露于乙醇，即，主要临床相关性的时间。事实上，胎儿和青少年接触酒精是成年人酗酒的关键危险因素。反过来，成年酗酒者产生胎儿酒精谱系障碍的儿童和青少年倾向于早期开始使用酒精。这增加了青少年发展酒精使用障碍的可能性，从而使这一循环持续下去。这种发展性的程序设计构成了我们所谓的“酒精中毒发生器”。“我们的发展暴露酒精研究中心（DEARC）的约束性主题是（1）乙醇影响神经系统发育中的神经适应，（2）乙醇诱导的效应取决于神经系统的发育阶段，（3）大脑发育改变乙醇效应的常见机制，反过来乙醇影响大脑发育。DEARC的主题结合了每个项目中提出的新假设。四个高度综合的主要项目将研究乙醇相关的发育缺陷的机制。这些项目是研究在产前/婴儿或青少年时期发育暴露于乙醇的影响（1）对神经干细胞和树突可塑性的命运，（2）对化学感觉功能和发育的经验诱导的可塑性，（3）对个体发育编程和年龄相关的积极和消极乙醇强化机制，（4）神经递质系统在酒精敏感性中的作用。高级酒精研究人员和发育神经生物学家将指导这些项目。这些研究人员之间协同互动的基础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学核心）。该中心将继续作为创意，新项目和研究人员成长的孵化器。这些活动的一个机制将是试点项目方案。拟议的试点项目将补充和扩大主要项目。作为一个单位，拟议中的中心将融合高级生物医学和行为研究人员的人才在三个校区的州立大学的纽约：宾厄姆顿大学在宾厄姆顿，纽约州立大学科特兰，和上州医科大学在锡拉丘兹。因此，该中心将作为纽约中部酒精研究的中心，并作为国家活动的灯塔。

DESCRIPTION (Provided by the applicant): 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.