Stress Hormone Enhancement of OP-Induced Neuroinflammation as an Animal Model of GWI: The Role of Toll-like Receptors and Plasticity
Abstract
Several chemicals and environmental conditions have been implicated in the exposures in theater that caused GWI. We have combined GW agent exposures with corticosterone (CORT) in the mouse to simulate physiological stresses in the war theater. The Morris water maze failed to provide evidence of an impairment in this paradigm. We switched to diisopropylfluorophosphate (DFP) as it was a stronger organophosphate inflammagen, and utilized novel object testing as more compatible with the mouse behavioral repertoire. In addition, we instituted a longer intermittent CORT administration with a single DFP dose, and used lipopolysaccharide (LPS) as an acute neuroimmune reactivator. We found evidence of cognitive impairment in mice in the novel object tests using both CORT administration regimens. These impairments persist until 12-14 days after DFP or LPS. However, the impairments were not present when separate animals were tested 60-63 days after exposures were terminated. Studies of cellular proliferation suggested that mice were in adrenocortical insufficiency at the time of behavioral testing after the 1 week CORT+DFP regimen ended. Preliminary work has indicated changes in gene expression of specific NMDA receptor subunits after CORT+DFP, but additional testing is necessary to understand the cellular basis of the CORT priming phenomenon and the role of neuroinflammation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2019
- Accession Number
- AD1095357
Entities
People
- Stephen M. Lasley
Organizations
- University of Illinois at Chicago