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Cannabidiol reverses microglial exhaustion in aged Gulf War Illness mice

ABSTRACT: Gulf War Illness (GWI) affects up to one-third of 1990–1991 Gulf War veterans and is associated with chronic low-grade neuroinflammation, yet its cellular substrates remain unclear and targeted pharmacological therapies are still limited. By using bulk RNA-seq analyses of FACS-purified microglia in an established GWI mouse model, we uncovered a multi-lineage primed neuroimmune signature in aged GWI mice. Systemic lipopolysaccharide (LPS) elicited an amplified pro-inflammatory response in the brains of GWI mice compared to age-matched controls, yet paradoxically, microglia were transcriptionally hyporesponsive to LPS, with inverted antigen presentation module score indicative of a microglial exhaustion phenotype. Chronic cannabidiol (CBD) attenuated neuroimmune priming at baseline, reshaping microglial translational and energetic states. Under immune-stimulated conditions, CBD partially restored GWI-associated deficits in microglial antigen presentation and oxidative phosphorylation, defining a therapeutic axis amenable to pharmacological intervention.

ORGANISM(S): Mus musculus

PROVIDER: GSE338200 | GEO | 2026/07/14

REPOSITORIES: GEO

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Cannabidiol reverses neuroimmune priming in aged Gulf War Illness mice

Project description:Gulf War Illness (GWI) affects up to one-third of 1990–1991 Gulf War veterans and is associated with chronic low-grade neuroinflammation, yet its cellular substrates remain unclear and targeted pharmacological therapies are still limited. By using bulk RNA-seq analyses of whole-brain in an established GWI mouse model, we uncovered a multi-lineage primed neuroimmune signature in aged GWI mice. Systemic lipopolysaccharide (LPS) elicited an amplified pro-inflammatory response in the brains of GWI mice compared to age-matched controls. Chronic cannabidiol (CBD) attenuated neuroimmune priming at baseline, and suppressed the parenchymal hyper-response, defining a therapeutic axis amenable to pharmacological intervention.

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