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脆弱的目标之一。与其他器官不同，大脑的发育需要很长时间。它从一开始（原肠胚期）、妊娠期、婴儿期和青春期就易受乙醇毒性的影响。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，因为他们是(1)大脑发育的关键和快速时期，(2)发育中的人类最有可能暴露于乙醇，即主要临床相关性时期。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，成年酗酒者会产生患有胎儿酒精谱系障碍的儿童和容易过早开始饮酒的青少年。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。这种发展程序构成了我们所称的“酗酒生成器”。我们的发育暴露酒精研究中心（DEARC）的结合主题是：(1)乙醇影响发育中的神经系统的神经适应性，(2)乙醇诱导的影响取决于神经系统的发育阶段，以及(3)大脑发育改变乙醇作用的共同机制，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。四个高度整合的主要项目将研究乙醇相关发育缺陷的机制。这些项目是关于在产前/婴儿或青少年时期暴露于乙醇对神经干细胞和树突可塑性的影响的研究(1)对神经干细胞和树突可塑性的命运的影响，(2)对化学感觉功能和发育中经验诱导的可塑性的影响，(3)对个体发育规划和年龄相关的正向和负向乙醇强化机制的影响，以及(4)神经递质系统在青少年典型乙醇敏感性中的作用。资深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作用的基础来自于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。建议的试验计划将补充和扩展主要计划。作为一个整体，拟议中的中心将融合纽约州立大学三个校区的高级生物医学和行为研究人员的才能：宾厄姆顿大学、纽约州立大学-科特兰分校和锡拉丘兹的上州医科大学。因此，研究中心将成为纽约中部酒精研究的纽带，并成为全国活动的灯塔。

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.