title: Reactivation of inflammatory bowel disease in a mouse model of depression.
abstract: OBJECTIVE
  Patients with inflammatory bowel disease (IBD) frequently also have depression, yet little is known of its role in IBD pathogenesis. We investigated whether the development of depression after the establishment of chronic inflammation reactivates an acute relapse of IBD and underlying pharmacologic mechanisms in mouse models.
  
  
  METHODS
  Colitis was induced by administration of dextran sulfate sodium (DSS) or dinitrobenzenesulfonic acid to C57BL/6 mice. Depression was induced by olfactory bulbectomy or chronic intracerebroventricular injection of reserpine. Colitis was reactivated by subsequent exposure to DSS or dinitrobenzenesulfonic acid. Some mice were given the antidepressant desmethylimipramine. Acute DSS-colitis was induced in mice lacking the alpha 7 subunit of the nicotinic acetylcholine receptor (alpha 7nAchR), and vagotomy was performed. Disease severity and colon tissue histology and inflammation were evaluated. Levels of C-reactive protein and proinflammatory cytokines were determined by enzyme-linked immunosorbent assay analysis of colon samples and macrophage culture.
  
  
  RESULTS
  Induction of depression reactivated inflammation in mice in which colitis had been established and become quiescent. The induction was associated with impaired cholinergic inhibition of proinflammatory cytokine secretion by macrophages and mediated by alpha 7nAchR on these cells; macrophages isolated from depressed mice showed increased proinflammatory cytokine secretion. Depression-induced reactivation of colitis was prevented by desmethylimipramine and accompanied by a normalization of proinflammatory cytokine secretion.
  
  
  CONCLUSIONS
  Depression reactivates dormant chronic colitis via the alpha 7nAchR. These findings encourage closer monitoring of behavior for signs of depression in IBD patients because treatment might prevent inflammatory conditions. Furthermore, alpha 7nAchR agonists might achieve this effect without the need for psychotropic medication.
authors.affiliation: Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jean-Eric
authors.initials: JE
authors.lastname: Ghia
authors.forename: Patricia
authors.initials: P
authors.lastname: Blennerhassett
authors.forename: Ykang
authors.initials: Y
authors.lastname: Deng
authors.forename: Elena F
authors.initials: EF
authors.lastname: Verdu
authors.forename: Waliul I
authors.initials: WI
authors.lastname: Khan
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Collins
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism*; D002478:Cells, Cultured; D003092:Colitis / Q000473:pathology* / Q000523:psychology*; D016207:Cytokines / Q000378:metabolism*; D003863:Depression / Q000139:chemically induced / Q000523:psychology*; D016264:Dextran Sulfate / Q000494:pharmacology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis; D015212:Inflammatory Bowel Diseases / Q000473:pathology / Q000523:psychology; D007413:Intestinal Mucosa / Q000166:cytology / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011336:Probability; D011897:Random Allocation; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D002097:C-Reactive Protein; D016264:Dextran Sulfate