GWI Mouse model SIDL - Complementary proteomic approaches reveal mitochondrial dysfunction, immune and inflammatory dysregulation in a mouse model of gulf war illness

Long term consequences of combined pyridostigmine bromide and permethrin exposure in C57BL6/J mice using a well characterized mouse model of exposure to these Gulf War agents. Expanding on earlier work, we used orthogonal proteomic approaches to identify pathways that are chronically impacted in the mouse CNS due to semi-acute GW agent exposure early in life. These analyses were performed on soluble and membrane-bound protein fractions from brain samples using two orthogonal isotopic labeling LC-MS/MS proteomic approaches – stable isotope dimethyl labeling (SIDL) and isobaric tags for relative and absolute quantitation (iTRAQ). The use of these approaches allowed for greater coverage of proteins than was possible by either one alone and revealed both distinct and overlapping datasets. This combined analysis identified changes in several mitochondrial, as well as immune and inflammatory pathways after GW agent exposure. The work discussed here provides insight into GW-agent exposure dependent mechanisms that adversely affect mitochondrial function and immune and inflammatory regulation at five months post exposure to PB+PER.