{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:38:59Z","timestamp":1790228339149,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,9,30]],"date-time":"2013-09-30T00:00:00Z","timestamp":1380499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:p>Gulf War illness (<jats:styled-content style=\"fixed-case\">GWI<\/jats:styled-content>) is a currently untreatable multi\u2010symptom disorder experienced by 1990\u20131991 Persian Gulf War (<jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>) veterans. The characteristic hallmarks of<jats:styled-content style=\"fixed-case\">GWI<\/jats:styled-content>include cognitive dysfunction, tremors, migraine, and psychological disturbances such as depression and anxiety. Meta\u2010analyses of epidemiological studies have consistently linked these symptomatic profiles to the combined exposure of<jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>agents such as organophosphate\u2010based and pyrethroid\u2010based pesticides (e.g. chlorpyrifos (<jats:styled-content style=\"fixed-case\">CPF<\/jats:styled-content>) and permethrin (<jats:styled-content style=\"fixed-case\">PER<\/jats:styled-content>) respectively) and the prophylactic use of pyridostigmine bromide (<jats:styled-content style=\"fixed-case\">PB<\/jats:styled-content>) as a treatment against neurotoxins. Due to the multi\u2010symptomatic presentation of this illness and the lack of available autopsy tissue from<jats:styled-content style=\"fixed-case\">GWI<\/jats:styled-content>patients, very little is currently known about the distinct early pathological profile implicated in<jats:styled-content style=\"fixed-case\">GWI<\/jats:styled-content>(including its influence on synaptic function and aspects of neurogenesis). In this study, we used preclinical models of<jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>agent exposure to investigate whether 6\u2010month\u2010old mice exposed to<jats:styled-content style=\"fixed-case\">CPF<\/jats:styled-content>alone, or a combined dose of<jats:styled-content style=\"fixed-case\">CPF<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">PB<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">PER<\/jats:styled-content>daily for 10 days, demonstrate any notable pathological changes in hippocampal, cortical (motor, piriform) or amygdalar morphometry. We report that at an acute post\u2010exposure time point (after 3 days), both exposures resulted in the impairment of synaptic integrity (reducing synaptophysin levels) in the<jats:styled-content style=\"fixed-case\">CA3<\/jats:styled-content>hippocampal region and altered neuronal differentiation in the dentate gyrus (<jats:styled-content style=\"fixed-case\">DG<\/jats:styled-content>), demonstrated by a significant reduction in doublecortin positive cells. Both exposures also significantly increased astrocytic<jats:styled-content style=\"fixed-case\">GFAP<\/jats:styled-content>immunoreactivity in the piriform cortex, motor cortex and the basolateral amygdala and this was accompanied by an increase in (basal) brain acetylcholine (<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>h) levels. There was no evidence of microglial activation or structural deterioration of principal neurons in these regions following exposure to<jats:styled-content style=\"fixed-case\">CPF<\/jats:styled-content>alone or in combination with<jats:styled-content style=\"fixed-case\">PB<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">PER<\/jats:styled-content>. Evidence of subtle microvascular injury was demonstrated by the reduction of platelet endothelial cell adhesion molecule (<jats:styled-content style=\"fixed-case\">PECAM<\/jats:styled-content>)\u20101 levels in<jats:styled-content style=\"fixed-case\">CPF<\/jats:styled-content>+<jats:styled-content style=\"fixed-case\">PB<\/jats:styled-content>+<jats:styled-content style=\"fixed-case\">PER<\/jats:styled-content>exposed group compared to control. These data support early (subtle) neurotoxic effects on the brain following exposure to<jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>agents.<\/jats:p>","DOI":"10.1111\/neup.12061","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T01:53:04Z","timestamp":1381542784000},"page":"109-127","source":"Crossref","is-referenced-by-count":73,"title":["Exposure to an organophosphate pesticide, individually or in combination with other<scp>G<\/scp>ulf<scp>W<\/scp>ar agents, impairs synaptic integrity and neuronal differentiation, and is accompanied by subtle microvascular injury in a mouse model of<scp>G<\/scp>ulf<scp>W<\/scp>ar agent exposure"],"prefix":"10.1111","volume":"34","author":[{"given":"Joseph O.","family":"Ojo","sequence":"first","affiliation":[{"name":"Roskamp Institute Sarasota Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"Abdullah","sequence":"additional","affiliation":[{"name":"Roskamp Institute Sarasota Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Evans","sequence":"additional","affiliation":[{"name":"Roskamp Institute Sarasota Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon Mike","family":"Reed","sequence":"additional","affiliation":[{"name":"Roskamp Institute Sarasota Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Montague","sequence":"additional","affiliation":[{"name":"Roskamp Institute Sarasota Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Mullan","sequence":"additional","affiliation":[{"name":"Roskamp Institute Sarasota Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona 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