Stress Hormone Enhancement of OP-induced Neuroinflammation as an Animal Model of GWI: The Role of Toll-like Receptors and Plasticity
Abstract
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 physiological/environmental 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 CORT+CPO and CORT+DDVP regimens in the GWI model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2020
- Accession Number
- AD1095500
Entities
People
- James P. O'Callaghan
- Kimberly A. Kelly
- Lindsay T. Michalovicz