Project 1 - Developmental Exposure Alcohol Research Center

中枢神经系统的发展需要很长一段时间;然而，有两次值得注意的 易受酒精毒性影响-在胎儿和青少年发育期间。这也是一个 因为许多人在胎儿和青少年时期接触酒精。的 胎儿和青少年正在进行的发育事件是完全不同的，因此，乙醇诱导的 变化也不同。定义为胎儿发育和青春期的精液事件 的细胞命运和树突状细胞的生长和细化。本研究将探讨的影响， 乙醇对这些过程的影响，通过检验以下假设：（1）乙醇通过改变 未确定的神经元祖细胞的命运，（2）乙醇影响重塑的突触连接 在青春期以时间依赖的方式，和（3）可塑性的青少年是由改变启动 在胎儿发育和青春期的这种变化建立长期的大脑结构的变化 在成人中。重点将是大脑皮层，因为它对学习等活动至关重要， 记忆和执行功能，公认的乙醇的行为目标。这些研究将利用 转基因小鼠具有选择的神经元群体，第V层的锥体神经元， 发荧光。研究将确定（1）胎儿乙醇暴露对神经元命运的影响， 转录因子Foxgl在这一过程中的作用，（2）青少年酒精暴露的影响 树突、棘和突触可塑性以及兴奋性和抑制性神经递质系统的作用 在可塑性方面，以及（3）胎儿和额外青少年暴露联合收割机是否结合起来， 大脑皮层结构的潜在永久性变化因此，本项目的目标是测试“酒精中毒 DEARC的核心假设是“生成器”假设--胎儿编程建立了成人大脑的结构 青少年接触乙醇会加剧这一过程。

The central nervous system develops over a protracted period; yet, there are two times of notable vulnerability to ethanol toxicity- during fetal and adolescent development. These are also times that are of critical clinical importance because many are exposed to alcohol during fetal and adolescent life. The ongoing developmental events in the fetus and adolescent are quite different, thus the potential for ethanolinduced changes also differ. Seminal events in fetal development and during adolescence are the definition of cell fate and dendritic growth and refinement, respectively. The present study will explore the effects of ethanol on these processes by testing the hypotheses that (1) ethanol affects CNS composition by altering the fates of undetermined neuronal progenitors, (2) ethanol affects synaptic connections that are remodeled during adolescence in a time-dependent manner, and (3) plasticity in the adolescent is primed by alterations in fetal development and that such changes in the adolescent establish long-term changes in brain structure in the adult. The focus will be the cerebral cortex because it is critical for activities such as learning, memory, and executive function, acknowledged behavioral targets of ethanol. These studies will exploit transgenic mice that have a select population of neurons, pyramidal neurons in layer V, that endogenously fluoresce. Studies will determine (1) the effects of fetal ethanol exposure on neuronal fate and the contribution of the transcription factor Foxgl in that process, (2) the effects of adolescent ethanol exposure on dendritic, spine, and synaptic plasticity and the role of excitatory and inhibitory neurotransmitter systems in that plasticity, and (3) whether fetal and additional adolescent exposure combine for greater and potentially permanent changes in cortical structure. Thus, the goal of this project is to test the "alcoholism generator" hypothesis central to the DEARC- that fetal programming sets up the structure of the adult brain and that this process is exacerbated by adolescent exposure to ethanol.