Impaired parasympathetic function increases susceptibility to inflammatory bowel disease in a mouse model of depression

Jean-Eric Ghia, Patricia Blennerhassett, and Stephen M. Collins

J. Clin. Invest. 118:2209–2218 (2008)

Speaker: Juin-Wei Chen (陳君瑋)                                          Time: 15:00~16:00, Oct. 1, 2008

Commentator: Dr. Chrong-Reen Wang (王崇任博士)                    Place: Room 601

Abstract:

Inflammatory bowel disease (IBD) is a idiopathic, chronic and relapsing inflammation disease of the gastrointestinal tract. There are some literatures indicating that intestinal inflammation severity may relate to behavior condition such as depression. However, the causation between depression and inflammatory response such as colitis remains unclear. In addition, it has been identified that vagus nerve plays an important role in retarding the inflammatory conditions via mediating of macrophages. Imbalanced vagus nerve could be speculated on leading to a worse situation of inflammation. Firstly, the authors adopted two models (DSS and DNBS treatment) to induce colitis collocating with reserpinizing the mouse, the model of depression, and discovered severe inflammation in the colon. After DSS colitis, vagotomy increased the severity resulting from decreasing the acetylcholine, the primary neurotransmitter of the parasympathetic system, concentration in the colon. Certainly, this condition was improved by treating nicotine, the parasympathomimetic agent. Furthermore, as for the critical target cell in related to vagal modulation of inflammation, in macrophage deficient mice (op/op, M-CSF deficient), many proinflammatory cytokines level didn’t increase in DSS colitis. Therefore, macrophages plays an important in inflammatory regulation. The authors at last introduce a tricyclic antidepressant ─ desmethylimipramine (DMI), and discovered that inflammation was improved in depression mice treated with DMI. They thought antidepressants may be a novel approach to treat IBD patients with depression.

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2. Jean E. G., et al. 2006. The vagus nerve: a tonic inhibitory influence associated with inflammatory bowel disease in a murine model. Gastroenterology. 130, 1743-1753