Gut–Brain Actions Underlying Comorbid Neuropsychiatric Disturb Associated With Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic relapsing and remitting disorder characterized by inflammation of the gastrointestinal tract and its associated with different neurological and psychiatric disorders, which are integrated among the extra-intestinal manifestation of this disease. In fact, epidemiological studies have shown an increased incidence of depression in patients with colitis, in which strong inflammation in the gut occurs. The possible mechanisms connecting gut inflammation and neuroinflammation in the brain could be via an increase in peripheral cytokines or via damaged nerve terminals in the gut. Recent evidence demonstrated that the gut-brain-axis has a central function in the perpetuation of IBS, and, for this reason it can be considered as a possible therapeutic target. N-Palmitoylethanolamine-oxazoline (PEA-OXA) possesses anti-inflammatory and potent neuroprotective effects. Although, recent studies have explained the neuroprotective properties of PEA-OXA, nothing is known about its effects on gut-brain axis during colitis. The aim of this study is to explore the mechanism and the effect of PEA-OXA on gut brain axis in mice subjected to experimental colitis induced by intracolonic administration of Dextran sulfate sodium. Daily orally administration of PEA-OXA 10 mg/kg daily o.s. was able to decrease body weight loss, macroscopic score and colon length and histology alteration after DSS induction. On the other hand was able to reduce histology modification and c-FOS expression in the hippocampus. Additionally, we demonstrate that PEA-OXA administration significantly increase neurogenesis and promoting neurotrophic grow factor release and decrease astroglial and microglial activation DSS-induced. Moreover, PEA-OXA, was able to decrease inflammatory marker in both hippocampus and colon. In conclusion, in our work, we demonstrate for the fort time the action of PEAOXA on gut-brain axis during in a model of DSS induced colitis.