Stress Hormone Enhancement of OP-induced Neuroinflammation as an Animal Model of GWI: The Role of Toll-like Receptors and Plasticity
Technical Report,31 Oct 2016,30 Sep 2019
CDC/NIOSH Morgantown United States
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GWI is a multi-symptom disorder with features similar to sickness behavior e.g., fatigue, depression, cognitive impairments, sleep disturbances, gastrointestinal problems. The exposures and conditions in theater that caused GWI remain unknown but several classes of chemicals and physiologicalenvironmental conditions have been implicated. We are working to expand upon our previously developed mouse model of GWI combining corticosterone CORT, as a stressor mimic, and DFP, a sarin surrogate. As such, we have tested the combination of chlorpyrifos oxon CPO with CORT in our long-term exposure paradigm. While the lower dose of CPO being employed in the behavioral experiments did not result in significant neuroinflammation, we have found significant alterations in Toll-like receptor signaling, as well as with the long-term DFP paradigm. Additionally, dose response studies have been performed to determine an appropriate dose for dichlorvos. In year 3, we will continue working with the CORTCPO and CORTDDVP regimens in the GWI model.
- Medicine and Medical Research