NEUROANATOMICAL/FUNCTIONAL CORRELATES IN FASD MODEL

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项拟议研究的总体目标是描述妊娠早期酒精暴露对小鼠大脑的长期影响。尽管有大量文献描述了酒精对神经系统发育的作用，但仍有许多东西需要了解，特别是关于怀孕早期接触酒精的影响。先前关于妊娠早期酒精暴露影响的研究(在相当于妊娠头三个月的部分时间)已证明对特定大脑区域(如小脑和海马体)有有害影响，并普遍存在躯体发育迟缓。到目前为止，研究的重点是乙醇畸形的产前表现，这些不良影响的长期发展概况仍未被探索。该提案中概述的工作将利用高分辨率磁共振成像(MRI)、扩散张量成像(DTI)和一系列行为测试，以更全面地检查C57BL/6J小鼠在妊娠第8天(GD)暴露于酒精的后遗症；先前的研究表明，暴露时间值得深入考虑。它假设，候选人观察到的和之前报告的在胎鼠身上发生的区域性缺陷将在出生后整个发育过程中保持不变，尽管躯体生长迟缓发生了逆转。本文提出的实验结果将极大地扩展我们对早期酒精暴露对大脑结构和功能的长期影响的知识。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of the proposed research is to characterize the long-term effects on the mouse brain resulting from early gestational ethanol exposure. In spite of the tremendous literature describing the actions of ethanol on the developing nervous system, there is still much to learn, especially regarding the effects of ethanol exposure during early periods of pregnancy. Previous studies examining the effects of early gestational ethanol exposure (during parts of the first trimester equivalent) have demonstrated detrimental effects on specific brain regions (e.g. the cerebellum and hippocampus) and a general somatic growth retardation. To date, research concentration has been on the prenatal manifestations of ethanol dysmorphogenesis, with the long-term developmental profile of these adverse effects remaining unexplored. The work outlined in this proposal will utilize high-resolution magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and a battery of behavioral tests to more fully examine the sequelae of ethanol exposure on gestational day (GD) 8 in C57Bl/6J mice; an exposure time which previous studies have shown to be worthy of in-depth consideration. It is hypothesized that the regional deficits observed and previously reported by the candidate to occur in fetal mice will remain throughout postnatal development, in spite of a reversal of the somatic growth retardation. The results of the experiments proposed herein will greatly expand our knowledge of the long-term effects of early ethanol exposure on both the structure and function of the brain.