Teratogenesis in the Developing Hippocampus

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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.