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Accession Number:
AD1098970
Title:
Neuropathological and Behavioral Sequelae in IL-1R1 and IL-1Ra Gene Knockout Mice After Soman (GD) Exposure
Descriptive Note:
Journal Article - Open Access
Corporate Author:
US Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground United States
Report Date:
2017-09-01
Pagination or Media Count:
15.0
Abstract:
Soman GD exposure results in status epilepticus SE that leads to neurodegeneration, neuroinflammation, and behavioral consequences including learning and memory deficits. The neuroinflammatory response is characterized by the upregulation of the pro-inflammatory cytokine, interleukin-1 IL-1, which mediates the expression of other neurotoxic cytokines induced after GD exposure. However, the specific role of IL-1 signaling has not been defined in terms of the consequences of GD-induced SE. Therefore, the purpose of this study was to regulate IL-1 signaling and study the behavioral deficits and neurodegeneration that occur after convulsion onset. Wild type WT, IL-1 receptor IL-1R1 knockout KO, and IL-1 receptor antagonist IL-1Ra KO mice were exposed to aconvulsive dose of GD, and behavior was evaluated up to 18 days later. Activity was studied using theOpen Field, anxiety was assessed in the Zero Maze, and spatial learning and memory were evaluated with the Barnes Maze. The animals were euthanized at 24 hours and 18 days to determine neuropathology inthe piriform cortex, amygdala, thalamus, and CA1, CA23, and CA4 regions of the hippocampus. Unlike the IL-1Ra KO, the IL-1R1 KO showed less neuropathology compared to WT at 24 hours, but moderate to severe injury was found in all strains at 18 days. Compared to their saline controls, the exposed WT micewere significantly more active in the Open Field, and the IL-1R1 KO strain showed reduced anxiety in theZero Maze Test. Compared to WT mice, IL-1R1 and IL-1Ra KO mice had spatial learning and memory impairments in the Barnes Maze. Therefore, the IL-1 signaling pathway affects neurodegeneration and behavior after GD-induced convulsions.
Distribution Statement:
APPROVED FOR PUBLIC RELEASE
