Teratogenesis in the Developing Hippocampus

描述（由申请人提供）：神经发育是大脑特别容易受到环境损害的时期。我计划使用甲基汞;一种已知的致畸剂，持续存在于我们的环境中，作为一种致畸工具来探测海马体的脆弱性。第一个目的是研究甲基汞对出生后第7天（P7）海马神经发生和细胞凋亡的影响，在体内和更深入的文化。接下来，我们将通过研究总DNA含量、面积形态测定和无偏体视学来表征青少年（P35）和成人（P60）海马中P7致畸诱导的细胞缺陷组织，以确定对特定神经元群体的影响。最后，我们将确定成人海马（P60）的认知功能后，急性致畸暴露在P7使用Morris水迷宫。然后对这些用于行为分析的动物进行DNA含量、面积形态测定和无偏体视学处理，并与未用于行为分析的溶剂和甲基汞处理动物（即未处理动物）进行比较。海马结构和功能的缺陷持续到成年期，这是可能接触这种致畸剂的公众关注的一个原因。这项研究将证明甲基汞对海马体的影响达到分子水平，这有助于理解、识别和治疗神经损伤。

DESCRIPTION (provided by applicant): Neurodevelopment is a time when the brain is particularly vulnerable to environmental insults. I plan to use methylmercury; a known teratogen that persists in our environment, as a teratogenic tool to probe hippocampal vulnerability. The first aim is to study MeHg's effects on postnatal day 7 (P7) hippocampal neurogenesis and apoptosis in vivo and in greater depth in culture. Next we will characterize tissue for cellular deficits induced by P7 teratogenesis in the adolescent (P35) and adult (P60) hippocampus with studies of total DNA content, area morphometry and unbiased stereology to define effects on specific neuronal populations. Finally, we will determine cognitive functions of the adult hippocampus (P60) after acute teratogenic exposure at P7 using the Morris water maze. These animals used for behavior will then be processed for DNA content, area morphometry and unbiased stereology and compared to both vehicle and MeHg treated animals not used for behavioral analysis (i.e. naive animals). Deficits in the structure and function of the hippocampus that persist into adulthood are a cause for concern to the general public that may be in contact with such a teratogen. This study will demonstrate the effects of MeHg on the hippocampus down to the molecular level, which can contribute to understanding, identifying and treating neurological insults.