Abstract
Cognitive dysfunction is amongst the most conspicuous symptoms in Gulf War illness (GWI). Combined exposure to the nerve gas antidote pyridostigmine bromide (PB), pesticides and stress during the Persian Gulf War-1 (PGW-1) are presumed to be among the major causes of GWI. Indeed, our recent studies in rat models have shown that exposure to GWI-related (GWIR) chemicals and mild stress for 4 weeks engenders cognitive impairments accompanied with several detrimental changes in the hippocampus. In this study, we tested whether reduced numbers of hippocampal gamma-amino butyric acid (GABA)-ergic interneurons are among the pathological changes induced by GWIR-chemicals and stress. Animals were exposed to low doses of GWIR-chemicals and mild stress for 4 weeks. Three months after this exposure, subpopulations of GABA-ergic interneurons expressing the calcium binding protein parvalbumin (PV), the neuropeptide Y (NPY) and somatostatin (SS) in the hippocampus were stereologically quantified. Animals exposed to GWIR-chemicals and stress for 4 weeks displayed reduced numbers of PV-expressing GABA-ergic interneurons in the dentate gyrus and NPY-expressing interneurons in the CA1 and CA3 subfields. However, no changes in SS+ interneuron population were observed in the hippocampus. Furthermore, GABA-ergic interneuron deficiency in these animals was associated with greatly diminished hippocampus neurogenesis. Because PV+ and NPY+ interneurons play roles in maintaining normal cognitive function and neurogenesis, and controlling the activity of excitatory neurons in the hippocampus, reduced numbers of these interneurons may be one of the major causes of cognitive dysfunction and reduced neurogenesis observed in GWI. Hence, strategies that improve inhibitory neurotransmission in the hippocampus may prove beneficial for reversing cognitive dysfunction in GWI.
Highlights
Almost 25–30% of 700,000 troops deployed to the Persian Gulf War-1 (PGW-1) are diagnosed with Gulf War illness (GWI), which is a chronic multi-symptom illness affecting multiple systems including the central nervous system (Binns et al, 2008, 2014; Golomb, 2008)
GWI-RATS DISPLAYED GREATLY REDUCED NUMBERS OF PV+ INTERNEURONS IN THE dentate gyrus (DG) Immunohistochemical staining of sections with an antibody against PV allowed examination of the distribution of PVexpressing gamma-amino butyric acid (GABA)-ergic interneurons in the DG and the CA1 and CA3 subfields of both naive control rats and GWI-rats (Figures 1A1,bar (A1) and (B1))
Stereological quantification revealed that GWI-rats displayed 50% reduction in the total number of PV+ interneurons in the DG, in comparison to naive control animals (p < 0.01, Figure 1C1)
Summary
Almost 25–30% of 700,000 troops deployed to the Persian Gulf War-1 (PGW-1) are diagnosed with Gulf War illness (GWI), which is a chronic multi-symptom illness affecting multiple systems including the central nervous system (Binns et al, 2008, 2014; Golomb, 2008). Cognitive and mood impairments are among the conspicuous brain-related symptoms in GWI veterans and in animal models of GWI (Haley et al, 2000a,b; Steele, 2000; Odegard et al, 2013; Parihar et al, 2013; Rayhan et al, 2013; Hattiangady et al, 2014). While PB pills were consumed daily for variable periods of time as a prophylactic agent against possible nerve gas agent attacks during the war, exposures to DEET (a mosquito repellant) and PM (an insecticide) have occurred because of their extensive use on the skin and/or uniforms with the intension of offsetting infectious diseases transmitted by insects and ticks in the desert region (Haley and Kurt, 1997; Binns et al, 2008, 2014; Institute of Medicine Gulf War and Health, 2010; Steele et al, 2012).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
