title: Gulf War agent exposure causes impairment of long-term memory formation and neuropathological changes in a mouse model of Gulf War Illness.
abstract: Gulf War Illness (GWI) is a chronic multisymptom illness with a central nervous system component such as memory deficits, neurological, and musculoskeletal problems. There are ample data that demonstrate that exposure to Gulf War (GW) agents, such as pyridostigmine bromide (PB) and pesticides such as permethrin (PER), were key contributors to the etiology of GWI post deployment to the Persian GW. In the current study, we examined the consequences of acute (10 days) exposure to PB and PER in C57BL6 mice. Learning and memory tests were performed at 18 days and at 5 months post-exposure. We investigated the relationship between the cognitive phenotype and neuropathological changes at short and long-term time points post-exposure. No cognitive deficits were observed at the short-term time point, and only minor neuropathological changes were detected. However, cognitive deficits emerged at the later time point and were associated with increased astrogliosis and reduction of synaptophysin staining in the hippocampi and cerebral cortices of exposed mice, 5 months post exposure. In summary, our findings in this mouse model of GW agent exposure are consistent with some GWI symptom manifestations, including delayed onset of symptoms and CNS disturbances observed in GWI veterans.
authors.affiliation: The Roskamp Institute, Sarasota, Florida, United States of America; The Open University, Walton Hall, Milton Keynes, Buckinghamshire, United Kingdom; James A. Haley Veteran's Hospital, Tampa, Florida, United States of America.
authors.forename: Zuchra
authors.initials: Z
authors.lastname: Zakirova
authors.affiliation: The Roskamp Institute, Sarasota, Florida, United States of America; The Open University, Walton Hall, Milton Keynes, Buckinghamshire, United Kingdom; James A. Haley Veteran's Hospital, Tampa, Florida, United States of America.
authors.forename: Miles
authors.initials: M
authors.lastname: Tweed
authors.affiliation: The Roskamp Institute, Sarasota, Florida, United States of America; The Open University, Walton Hall, Milton Keynes, Buckinghamshire, United Kingdom.
authors.forename: Gogce
authors.initials: G
authors.lastname: Crynen
authors.affiliation: The Roskamp Institute, Sarasota, Florida, United States of America; James A. Haley Veteran's Hospital, Tampa, Florida, United States of America.
authors.forename: Jon
authors.initials: J
authors.lastname: Reed
authors.affiliation: The Roskamp Institute, Sarasota, Florida, United States of America; The Open University, Walton Hall, Milton Keynes, Buckinghamshire, United Kingdom; James A. Haley Veteran's Hospital, Tampa, Florida, United States of America.
authors.forename: Laila
authors.initials: L
authors.lastname: Abdullah
authors.affiliation: University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Nadee
authors.initials: N
authors.lastname: Nissanka
authors.affiliation: The Roskamp Institute, Sarasota, Florida, United States of America.
authors.forename: Myles
authors.initials: M
authors.lastname: Mullan
authors.affiliation: The Roskamp Institute, Sarasota, Florida, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mullan
authors.affiliation: The Roskamp Institute, Sarasota, Florida, United States of America; The Open University, Walton Hall, Milton Keynes, Buckinghamshire, United Kingdom.
authors.forename: Venkatarajan
authors.initials: V
authors.lastname: Mathura
authors.affiliation: The Roskamp Institute, Sarasota, Florida, United States of America; The Open University, Walton Hall, Milton Keynes, Buckinghamshire, United Kingdom; James A. Haley Veteran's Hospital, Tampa, Florida, United States of America.
authors.forename: Fiona
authors.initials: F
authors.lastname: Crawford
authors.affiliation: The Roskamp Institute, Sarasota, Florida, United States of America; The Open University, Walton Hall, Milton Keynes, Buckinghamshire, United Kingdom; James A. Haley Veteran's Hospital, Tampa, Florida, United States of America.
authors.forename: Ghania
authors.initials: G
authors.lastname: Ait-Ghezala
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D015870:Gene Expression; D047830:Gulf War; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects*; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D026023:Permethrin / Q000633:toxicity*; D018923:Persian Gulf Syndrome / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D011729:Pyridostigmine Bromide / Q000633:toxicity*; D016708:Synaptophysin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D016708:Synaptophysin; C569015:Syp protein, mouse; D026023:Permethrin; D011729:Pyridostigmine Bromide