Developmental Exposure Alcohol Research Center

发育中的神经系统是乙醇最脆弱的目标之一。与其他器官不同，大脑的发育需要很长一段时间。它从一开始(原肠形成时)，一直到妊娠、婴幼儿和青春期，都对乙醇中毒敏感。我们将重点关注胎儿/新生儿和青春期酒精暴露的影响，因为它们是(1)大脑发育关键和快速的时期，(2)在发育过程中，人类最有可能暴露在乙醇中，即与临床最相关的时期。事实上，胎儿和青少年接触酒精是成年人酗酒的关键风险因素。反过来，成年酗酒者会生出患有胎儿酒精谱系障碍的儿童和青少年，容易很早就开始饮酒。这增加了青少年对酒精使用障碍的易感性，从而使这种循环永久化。这种发育程序构成了我们所称的“酒精中毒产生器”。我们的发展暴露酒精研究中心(DEARC)的约束性主题是(1)乙醇影响发育中神经系统的神经适应，(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共同机制，反过来，乙醇影响大脑发育。 DARC的主题将每个项目中提出的新假设联系在一起。四个高度集成的主要项目将研究与酒精相关的发育缺陷的机制。这些项目是关于在产前/婴幼儿或青春期期间发育暴露于酒精的影响(1)对神经干细胞的命运和树突可塑性的影响，(2)对经验诱导的化学感觉功能和发育的可塑性的影响，(3)对个体发育编程和正负乙醇强化的年龄相关机制的影响，以及(4)对神经递质系统在青少年-典型的酒精敏感性中的作用的影响。资深酒精研究人员和发育神经生物学家将指导这些项目。支撑这些研究人员之间协同互动的润滑剂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学核心)。该中心将继续作为创意、新项目和调查人员成长的孵化器。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，拟建的中心将整合纽约州立大学三个校区的高级生物医学和行为学研究人员的人才：宾厄姆顿的宾厄姆顿大学、纽约州立大学科特兰分校和锡拉丘兹的北部州立医科大学。因此，该中心将成为纽约市中心酒精研究的纽带，并成为全国活动的灯塔。

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.