title: Proteomic CNS profile of delayed cognitive impairment in mice exposed to Gulf War agents.
abstract: Gulf War Illness (GWI) is a chronic multisymptom condition with a central nervous system (CNS) component, for which there is no treatment available. It is now believed that the combined exposure to Gulf War (GW) agents, including pyridostigmine bromide (PB) and pesticides, such as permethrin (PER), was a key contributor to the etiology of GWI. In this study, a proteomic approach was used to characterize the biomolecular disturbances that accompany neurobehavioral and neuropathological changes associated with combined exposure to PB and PER. Mice acutely exposed to PB and PER over 10 days showed an increase in anxiety-like behavior, psychomotor problems and delayed cognitive impairment compared to control mice that received vehicle only. Proteomic analysis showed changes in proteins associated with lipid metabolism and molecular transport in the brains of GW agent-exposed mice compared to controls. Proteins associated with the endocrine and immune systems were also altered, and dysfunction of these systems is a prominent feature of GWI. The presence of astrogliosis in the GW agent-exposed mice compared to control mice further suggests an immune system imbalance, as is observed in GWI. These studies provide a broad perspective of the molecular disturbances driving the late pathology of this complex illness. Evaluation of the potential role of these biological functions in GWI will be useful in identifying molecular pathways that can be targeted for the development of novel therapeutics against GWI.
authors: Roskamp Institute, 2040 Whitfield Ave, Sarasota, FL, 34243, USA. labdullah@rfdn.org
authors: Laila
authors: L
authors: Abdullah
authors: Gogce
authors: G
authors: Crynen
authors: Jon
authors: J
authors: Reed
authors: Alex
authors: A
authors: Bishop
authors: John
authors: J
authors: Phillips
authors: Scott
authors: S
authors: Ferguson
authors: Benoit
authors: B
authors: Mouzon
authors: Myles
authors: M
authors: Mullan
authors: Venkatarajan
authors: V
authors: Mathura
authors: Michael
authors: M
authors: Mullan
authors: Ghania
authors: G
authors: Ait-Ghezala
authors: Fiona
authors: F
authors: Crawford
mesh_terms: D000208:Acute Disease; D000818:Animals; D001007:Anxiety / Q000139:chemically induced; D001692:Biological Transport / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism*; D003072:Cognition Disorders / Q000139:chemically induced*; D004703:Endocrine System / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000009:adverse effects; D007107:Immune System / Q000187:drug effects; D007306:Insecticides / Q000009:adverse effects; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D026023:Permethrin / Q000009:adverse effects; D018923:Persian Gulf Syndrome / Q000378:metabolism*; D040901:Proteomics; D011597:Psychomotor Performance / Q000187:drug effects; D011729:Pyridostigmine Bromide / Q000009:adverse effects; D014728:Veterans / Q000523:psychology
chemical_list: D004791:Enzyme Inhibitors; D007306:Insecticides; D026023:Permethrin; D011729:Pyridostigmine Bromide