Basic—Alimentary TractChronic Gastrointestinal Inflammation Induces Anxiety-Like Behavior and Alters Central Nervous System Biochemistry in Mice
Section snippets
Animals
Male BALB/c or AKR mice (Harlan, Mississauga, ON, Canada) were purchased at the age of 6–8 weeks and housed in a conventional specific pathogen-free unit at McMaster University Central Animal Facility. All experiments were conducted in accordance with the guidelines of the Canadian Council on Animal Care and received approval from the McMaster University Animal Research Ethics Board. A group of mice (n = 24) underwent subdiaphragmatic vagotomy, as described previously.31 Briefly, after
Assessment of Inflammation
T muris infection induced mild to moderate chronic colitis affecting mainly the cecum and the proximal colon. Macroscopically, the cecum appeared edematous with mild erythema, but no ulcers or erosions were noted. MPO values in infected mice treated with placebo were significantly higher compared with uninfected controls (Figure 1). The chronic inflammatory infiltrate was increased in infected mice compared with controls. Treatment with etanercept or budesonide tended to decrease MPO values and
Discussion
We show that chronic infection associated with mild gut inflammation caused by the noninvasive parasite T muris induces anxiety-like behavior in mice. Chronic inflammation was modest in severity and was not associated with macroscopic tissue damage such as ulceration. We show that abnormal behavior in T muris colitis was associated with decreased levels of hippocampal BDNF. Circulating proinflammatory cytokines and kynurenine were mildly, but significantly, increased and proteomic analysis
Acknowledgments
The authors are grateful to Mrs Jeannette Pearce for the technical support.
P.B. and E.F.V. contributed equally to this manuscript.
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Conflicts of interest These authors disclose the following: Drs Corthesy-Theulaz, Cherbut, and Bergonzelli are employees of Nestle, Switzerland. The remaining authors disclose no conflicts.
Funding This work was supported by grants from Canadian Institutes of Health Research (S.M.C., P.B.), Nestle (S.M.C., E.F.V.), Crohn's & Colitis Foundation of Canada (P.B., S.M.C.), and Advanced Foods and Materials Network (S.M.C., P.B., E.F.V.). E. F. Verdu is partially supported by grants from Canadian Association of Gastroenterology/CIHR. P. Bercik and E. F. Verdu hold Internal Career Awards by the Department of Internal Medicine, McMaster University.