Altered hippocampal function and cytokine levels in a rat model of Gulf War illness

LIFE SCIENCES

卷:274

Article

Gargas, Nathan M.^1,2,3  Ethridge, Victoria T.^1,4  Miklasevich, Molly K.^1,2  Rohan, Joyce G.¹ 

[1] Naval Med Res Unit Dayton, 2728 Q St,Area B,Bldg 837, Wright Patterson AFB, OH 45433 USA

[2] Henry M Jackson Fdn Adv Mil Med, 6720A Rockledge Dr, Bethesda, MD 20817 USA

[3] Odyssey Syst Consulting Grp Ltd, 201 Edgewater Dr Suite 270, Wakefield, MA 01880 USA

[4] Oak Ridge Inst Sci & Educ, 1299 Bethel Valley Rd, Oak Ridge, TN 37830 USA

关键词: Gulf War illness;    Hippocampus;    Glutamate;    Cytokines;    Electrophysiology;   

DOI  :  10.1016/j.lfs.2021.119333

来源: Elsevier

【 摘 要 】

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. Naive 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-1 beta. 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.

【 授权许可】

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