Epigenetic Mediation of Endocrine and Immune Response in an Animal Model of Gulf War Illness

There are now compelling human epidemiological and animal experimental data that indicate the risk of developing complex diseases is influenced by persistent epigenetic adaptations in response to environmental exposures such as toxins and stress. We propose to examine the epigenomic response to diisopropyl fluorophosphates DFP, a sarin surrogate, and associated changes to the immune and endocrine response to lipopolysaccharide LPS challenge in a mouse model of Gulf War Illness GWI, with stress hormone exposure as an experimental mediator. We will study the relationship between changes in DNA methylation and chromatin modifications in peripheral blood and the brain specifically hippocampus and prefrontal cortex in order to pursue a mechanistic understanding of the underlying pathology of GWI. During this reporting period, we have begun data collection on DNA methylation modifications and gene expression profiles in the brains of mice exposed to saline control, corticosterone and DFP, and have developed and refined protocols for this project in line with the GWIRC sister project.