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Altered hippocampal function and cytokine levels in a rat model of Gulf War illness
Nathan M Gargas1, Victoria T Ethridge2, Molly K Miklasevich3
1Naval Medical Research Unit Dayton, 2728 Q Street, Area B, Building 837, WPAFB, OH 45433, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD 20817, USA; Odyssey Systems Consulting Group, Ltd, 201 Edgewater Drive Suite 270, Wakefield, MA 01880, USA.
Aims:
Gulf War illness (GWI) is a disorder affecting military personnel deployed in the Gulf War (GW) from 1990 to 1991. Here, we will use a rat model of GWI to evaluate hippocampal function and cytokine levels.
Materials And Methods:
Rats were exposed to diethyltoluamide and permethrin via dermal absorption and pyridostigmine bromide via gavage with or without a 5-min restraint for 28 days. Immediate and delayed effects of GW chemical exposure were evaluated using electrophysiology to quantitate hippocampal function, behavioral tests to assess cognitive effects and biochemical assays to measure neurotransmitter and cytokine levels.
Key Findings:
Behavioral data revealed a statistically significant increase in motor activity at 3 months following completion of exposures, potentially indicating increased excitability, and/or restlessness. Electrophysiology data revealed statistically significant changes in paired pulse facilitation and input-output function of CA1 hippocampal neurons within 24 h and 3 months following completion of exposures. There was also a statistically significant reduction in the frequency of spontaneous firing activity of hippocampal neurons within 24 h following exposures. Naïve hippocampal slices directly incubated in GW chemicals also resulted in similar changes in electrophysiological parameters. Biochemical measurements revealed reduced hippocampal glutamate level at 3 months post-exposure. Furthermore, there was a statistically significant increase in plasma and hippocampal levels of IL-13, as well as decrease in plasma level of IL-1β.
Significance:
Our data support an effect on glutamate signaling within the hippocampus as indicated by changes in PPF and hippocampal level of glutamate, with some activation of T helper type 2 immune response.
