Functional implications of stress-evoked changes in epigenetic mechanisms

Tulane University, New Orleans LA

Investigators

Abstract

Prolonged or repeated stress leads to allostatic overload that mediates various cellular changes in the hippocampus, the area of the brain important for learning and memory. These changes result in reduced hippocampus function and deficits in learning and memory. Chronic stress-mediated memory deficits in humans and animals are well documented. Less is known about the molecular mechanisms underlying adverse effects that cause reduced hippocampus function in response to chronic stress. It is becoming increasingly evident that dynamic changes to the histones, the proteins that DNA is coiled around, are molecular mechanisms important for the physiological reaction to environmental stressors. Deciphering information encoded in histone modifications in the hippocampus in response to chronic stress is critical for understanding the molecular mechanisms of regulation of memory by stress. This project will identify novel histone changes that are modulated in response to chronic stress and negatively impact hippocampus function. Furthermore, the project is designed to investigate the effects on memory as the functional output of these modifications. By studying epigenetic changes and the mechanisms of these changes, these studies will define a novel common point of convergence as a mechanism to control transcription of genes that are regulated by stress and involved in learning and memory. Such information will fill the gap connecting histone modifications in the hippocampus to memory impairments caused by chronic stress. Students working in this lab will gain valuable research experience at the undergraduate, masters, and doctoral levels. These students participate in experiment planning, performance and analysis, as well as manuscript preparation and presentation at national and international meetings. Training provided by the research in this proposal is particularly important for science education in Louisiana, which is currently designated as an NSF EPSCOR state.