Genetic Basis of Individual Differences in Susceptibility to Gulf War Illness
Abstract
Background: Around 700,000 troops were deployed in Operation Desert Storm, the first Gulf War, and many, but not all, Soldiers returned with Gulf War Illness (GWI), a recurring, debilitating condition that persists to this day some 20 years after the war ended. Unfortunately, to date there is little understanding of the cause of GWI and likely the reason there are no truly effective treatments. The symptoms of GWI strikingly resemble those of ?sickness? behavior ? the set of symptoms that we all exhibit when we have a cold, the flu, or other illnesses. GWI Veterans have repeated ?flares? or bouts of sickness behavior, often in response to what seem like minor insults. The brain plays a major role in generating ?sickness? behavior as this organ recognizes the presence of the invading organisms and sets in motion the generation of these symptoms that help the victim regain health. These include lack of motivation to eat, move, or engage in other pleasurable activities as well as problems thinking, a desire to sleep, and vague diffuse aches and pain. Rationale: Although the Gulf has seen the deployment of many other Soldiers, they have not returned with GWI. GWI is specific to Operation Desert Storm, suggesting that these Soldiers might have been exposed to a unique set of circumstances (stressors) and chemicals (nerve gas, nerve gas prophylactics, pesticides, etc.). To test this idea, we have developed a mouse model of GWI by exposing mice to DFP, a nerve gas mimic, and corticosterone, the main hormone released by rodents when confronted by a stressor like a predator. Mice exposed and then challenged with an agent that causes sickness behavior exhibit greatly enhanced symptoms and changes in brain than mice not given DFP and CORT. Objective: As noted, not all Soldiers in the Desert Storm conflict developed GWI, although it is likely they all received similar exposures. We are trying to determine why and are speculating that our genes may play a role. Although all humans have many genes in common, we are not identical and display many differences in the full profile of individual genes (i.e., our genome). To develop our model, we used one type of mouse in which all the mice have almost identical genomes. Here we are using many sets (approximately 100) of mice that differ widely in the genes found in their genomes, known as recombinant inbred strains. If genes play a role in determining who develops GWI, when we give these mice the combination of DFP and CORT, we expect to see a range of symptoms and brain changes ranging from minimal to very large symptoms of sickness behavior. If we see a range of changes, we have tools that will allow us to quickly identify genes that are involved in these differences. Contributions: Once we have identified the possible genes involved in mice, we will be able to find out how they affect the way a person responds to the exposures. This helps us identify mechanisms and can lead to effective treatments.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710472
Entities
People
- Byron C Jones
Organizations
- United States Army
- University of Tennessee Health Science Center