Teratogenesis in the Developing Hippocampus

发育中的海马体的致畸

基本信息

批准号：
7933772
负责人：
Katie Sokolowski
金额：
$ 2.68万
依托单位：
UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7933772
关键词：
ARHGEF5 gene Acute Adolescent Adult Affect Aftercare Age Animals Apoptosis Apoptotic Area Astrocytes Behavior Behavioral Brain CDKN1C gene CSPG4 gene Caspase Inhibitor Cell Count Cell Culture Techniques Cell Cycle Cell Death Cells Cellular Structures Cerebellum Chemicals Collaborations Cyclin D1 Cyclin E Cytochromes DNA biosynthesis Development Environment Event Fibroblast Growth Factor 2 Financial compensation General Population Genetic Glial Fibrillary Acidic Protein Growth Factor Hand functions Hippocampus (Brain)Human In Vitro Injection of therapeutic agent Interleukin-2 Lead Learning Link Mediating Methylmercury Compounds Mitochondria Modeling Molecular Morphology Neuroglia Neurologic Neurons Organ Size Pathway interactions Performance Perinatal Ploidies Population Process Proteins Publishing Rat-1 Rattus Recovery of Function Regulation Role Signal Transduction Sprague-Dawley Rats Staining method Stains Stem cells Structure System Techniques Teratogens Third Pregnancy Trimester Time Tissues Training Water Western Blotting Work adult neurogenesis calbindin caspase-3 caspase-8 caspase-9 cell type cognitive function cyclin-dependent kinase inhibitor 1B dentate gyrus in vitro Model in vivo in vivo Model inhibitor/antagonist migration morphometry morris water maze nestin protein neurodevelopment neurogenesis postnatal relating to nervous system subcutaneous tissue processing tool toxicant

项目摘要

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.

描述（由申请人提供）：神经发育时期是大脑特别容易受到环境侵害的时期。我打算使用甲基汞；一种已知的致畸剂，存在于我们的环境中，作为探测海马体脆弱性的致畸工具。第一个目标是在体内和培养中更深入地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。接下来，我们将通过总 DNA 含量、面积形态测量和无偏立体学研究来表征青少年 (P35) 和成人 (P60) 海马中 P7 致畸引起的细胞缺陷组织，以确定对特定神经元群体的影响。最后，我们将使用 Morris 水迷宫测定 P7 急性致畸暴露后成人海马 (P60) 的认知功能。然后对这些用于行为的动物进行 DNA 含量、面积形态测量和无偏立体学处理，并与未用于行为分析的媒介物和甲基汞处理的动物（即幼稚动物）进行比较。海马结构和功能的缺陷持续到成年期，引起了可能与这种致畸剂接触的公众的担忧。这项研究将在分子水平上证明甲基汞对海马体的影响，这有助于理解、识别和治疗神经损伤。