NEUROANATOMICAL/FUNCTIONAL CORRELATES IN FASD MODEL

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 拟议研究的总体目标是描述妊娠早期乙醇暴露对小鼠大脑的长期影响。尽管有大量的文献描述了乙醇对发育中的神经系统的作用，但仍有很多东西需要学习，特别是关于怀孕早期乙醇暴露的影响。先前研究妊娠早期乙醇暴露的影响（相当于前三个月的部分时间）已经证明对特定脑区（如小脑和海马）和一般躯体生长迟缓的有害影响。到目前为止，研究集中在乙醇畸形的产前表现，这些不良影响的长期发展概况尚未探索。本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，更全面地检查C57 Bl/6 J小鼠妊娠第8天（GD）乙醇暴露的后遗症;先前的研究表明，暴露时间值得深入考虑。据推测，尽管体细胞生长迟缓逆转，但在胎鼠中观察到和先前报告的候选动物出现的区域缺陷将在整个出生后发育过程中保持。本文提出的实验结果将大大扩展我们对早期乙醇暴露对大脑结构和功能的长期影响的认识。

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.