Figure 8
Gulf War chemicals dysregulate peroxisomal lipid metabolism in astroglia, contributing to microglia activation and inflammation which corresponds with neurobehavioral deficits. Our working hypothesis is that GW chemicals affect peroxisomal lipid metabolism in the astrocytes since astroglia activation occurs earlier than microglia activation in this GWI mouse model. We also propose that the failure of astroglia to perform its neuroprotective function contributes to the subsequent activation of microglia and neuroinflammation. Targeting peroxisomes with OEA is expected to reduce astroglia activation which corresponds with normalization of peroxisomal lipid metabolism. We also propose that OEA may also reduce NFκB activation in microglia, thereby reducing neuroinflammation. In another scenario, OEA may undergo degradation by FAAH and oxygenation by other enzymes, generating additional bioactive metabolites which may target the cannabinoid receptors and also promote anti-inflammatory responses via synergistic activation of NFκB.
