There are nearly 250,000 Gulf War (GW) veterans who suffer from Gulf War Illness (GWI), a multi-symptom condition that remains untreatable. The main objective was to determine if targeting peroxisomal function could be of therapeutic value in GWI. We performed a pilot study that showed accumulation of very long chain fatty acids (VLCFA), which are metabolized in peroxisomes, in plasma from veterans with GWI. We then examined if targeting peroxisomal β-oxidation with oleoylethanolamide (OEA) restores these lipids to the normal levels and mitigates neuroinflammation and neurobehavioral deficits in a well-established mouse model of GWI. In GWI mice, treatment with OEA corresponded with cognitive benefits and reduced fatigue and disinhibition-like behavior in GWI mice. Biochemical and molecular analysis of the brain tissue showed reduced astroglia and microglia staining, decreased levels of chemokines and cytokines, and decreased NFκB phosphorylation. Treatment with OEA reduced accumulation of peroxisome specific VLCFA in the brains of GWI mice. These studies further support the translational value of targeting peroxisomes. We expect that OEA may be a potential therapy for treating neurobehavioral symptoms and the underlying lipid dysfunction and neuroinflammation associated with GWI. Oleoylethanolamide is available as a dietary supplement, making it appealing for human translational studies.
When compared with controls, ACC patients perform poorly in several tests. The callosotomy patient also showed evidence of impairment similar to that of the ACC patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.