P2X7 receptor blockade improves depressive-like behavior in mice subjected to a chronic model of inflammatory bowel disease

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B205
Abstract ID: 5979

Presenting Author:
Luiz Eduardo Baggio Savio , Assistant Professor at Univ. Fed. de Rio de Janeiro

Abstract:

Inflammatory bowel diseases (IBD) are multifactorial disorders characterized by chronic intestinal inflammation. IBD patients commonly have psychiatric disorders, including depression. Adenosine triphosphate (ATP) is a potent alarmin released by cellular stress/inflammation that modulates immune responses. ATP can activate P2X7 receptor, widely expressed in immune cells and central and enteric nervous systems. This receptor may contribute to IBD pathology. Here, we sought to investigate the role of P2X7 receptor in colitis-induced behavioral changes in mice. Chronic colitis was induced in C57Bl/6 mice (8-10 weeks) using 2% dextran sodium sulfate (DSS) diluted in water. Mice received Intraperitoneally the selective P2X7 receptor antagonist Brilliant Blue G (BBG - 50 mg/kg). Behavioral tests and molecular and cellular analyses were performed. DSS-treated animals showed increased P2X7 receptor amounts in the gut. DSS-BBG animals showed smaller and slower weight loss than the control group (DSS-vehicle). Colitis also increased the GFAP (glial fibrillary acidic protein) and p-CREB1 in the gut. BBG treatment reverted these effects. BBG also decreased the population of Tregs and Th17 cells in mice with colitis. The tail suspension test showed a colitis-induced depressive-like behavior, which was prevented by BBG treatment. Therefore,  P2X7 receptor inhibition can improve colitis-induced inflammation and depressive-like behavior in mice.