The University of Georgia
College of Veterinary Medicine
Class of 2019
Dysregulated splenic monoamine metabolism in a Gulf War Illness model: modulation by a neoglycoconjugate
Hannah E Gordon, Jessica M Carpenter, Donald A Harn, John J Wagner, and Nikolay M Filipov
Departments of Physiology and Pharmacology (Gordon, Carpenter, Wagner, Filipov) and Department of Infectious Diseases (Harn), College of Veterinary Medicine, University of Georgia, Athens, GA.
Gulf War Illness (GWI) is a chronic multisymptom illness affecting > 25% of the 1990-1991 GW veterans of unknown etiology, but likely caused by deployment-related chemical exposures, i.e., pyridosigmine bromide (PB, a nerve agent prophylactic), numerous pesticides, including DEET, sprayed regularly on the grounds and on uniforms, and the nerve agent sarin (by personnel stationed near the Khamisiya burn pits). Additionally, GW soldiers were subjected to the stressful war environment, manifested as increased corticosteroid levels. Some of the GWI symptoms might be related to autonomic dysfunction and resultant immune dysregulation due to altered peripheral monoamine, i.e., norepinephrine (NE) and serotonin (5-HT), homeostasis. Using a mouse model of GWI where mice were exposed to a combination of PB, DEET and corticosterone followed by a challenge with the sarin surrogate diisopropyl fluorophosphate (DFP), the effects of these GWI chemicals on splenic NE and 5-HT metabolism and the potential protective effects of a novel therapeutic, the neoglycoconjugate LNFPIII, were investigated 6 or 48h after the DFP challenge. Using high performance liquid chromatography splenic NE, its metabolite MHPG, 5-HT and its metabolite 5-HIAA were measured. GWI treatment increased 5-HT and NE at 6 and 48h independent of LNFPIII; 5-HIAA (statistically) and MHPG (numerically) were increased by both GWI treatment and LNFPIII at 6h, but not 48h, with the greatest metabolite increases seen in the GWI treatment/LNFPIII combination. Thus, it appears that the GWI treatment leads to lasting increased demands for splenic NE and 5-HT that are compensated by LNFPIII via increased monoamine metabolism at the earlier time point.
Research Grant: GWI150195 (Department of Defense; CDMRP)
Student Support: NIH Office of Research Infrastructure Programs, Grant Number 2T35OD010433-11