Neuroinflammatory gene expression changes in the brain in a rat model of Gulf War Illness – effects of rosiglitazone

Gulf War Illness (GWI) is a diverse set of neurologic and systemic symptoms affecting many veterans deployed in the Persian Gulf War, but its etiology is unknown and treatment options are limited. Veterans with GWI were exposed to a variety of agents, including pyridostigmine bromide, used as prophylaxis against nerve agents, intranasal lipopolysaccharide (LPS) from desert sandstorms, and chronic unpredictable stress (CUS) from combat. Here, we investigated the gene expression effects of these three Gulf War-related exposures (GWE) in adult rat frontal cortex (FC) and lateral amygdala (LA) using Clariom S microarrays. We found 138 transcript clusters (TCs) in LA and 38 TCs in FC differentially expressed between the group with GWE (n=2) compared to naïve controls (n=3, FDR <10%). These TCs included genes involved in inflammation such as Fosb (pmin=1.02e-5) and Junb (pmin=1.13e-5). Gene ontology analysis found enrichment of differentially expressed genes in “T cell differentiation” (pmin=8.71e-5) and “response to organophosphorus” (pmin=1.74e-8), among other categories. Lastly, we found that prophylactic treatment with rosiglitazone, a PPAR- agonist, reduced gene expression changes associated with GWE (in LA: 115/138 [83.3%] TCs with reduced changes, χ2=61.33, p=4.82e-15). These results suggest our rat model of GWI is associated with gene expression changes related to neuroinflammation and that some of these molecular changes may be mitigated by rosiglitazone prophylaxis. Control (N=3), Gulf War exposure (N=2) and Gulf War exposure with rosiglitazine prophylaxis (N=3) samples from dissection of rat lateral amygdala (LA) and frontal cortex (FC). Please refer to the corresponding publication for additional details.