Aryl hydrocarbon receptor ligand supplementation impacts colitis-associated depressive-like behavior

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B207
Abstract ID: 7399

Presenting Author:
Raymond K Bogdon , Graduate research assistant at Univ. of South Carolina Sch. of Med., Columbia

Abstract:

Colitis is an inflammatory bowel disease (IBD) with increased incidences of depression in patients. The mechanisms that define this comorbidity remain poorly understood. Our lab previously showed supplementation with indole-3-carbinol (I3C), an aryl hydrocarbon receptor (AhR) ligand, can reduce disease severity in models of colitis. We aimed to determine the behavioral impact I3C supplementation has on colitis-induced depression via alterations in the gut metabolome. Colitis was induced in using the dextran sodium sulfate (DSS) method and treatment groups were given a regimen of 40 mg/kg I3C as previously reported. Untargeted metabolomic studies revealed quinolinic acid (QA), a metabolite produced by the kynurenine (KYN) pathway and linked to depression, was found to be significantly reduced in I3C-treated mice when compared to colitis controls. To determine the effects of I3C and QA modulation on depressive-like behavior, colitis mice were treated with either I3C or an inhibitor of a major enzyme involved in QA production. Depressive-like behavior was measured using the Tail Suspension Test (TST) method, along with evaluation of neural biomarkers of depression (dopamine, BDNF, GFAP) and stabilization of the blood brain barrier (BBB). Results showed I3C reduced depressive-like behavior and altered select biomarkers associated with depression. These studies provide evidence that AhR can be a potential therapeutic target for both colitis and colitis-associated depression.