Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium

Department of Pharmacy Practice, School of Pharmacy, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Physiology & Behavior (Impact Factor: 2.98). 11/2006; 89(3):350-7. DOI: 10.1016/j.physbeh.2006.06.019
Source: PubMed


Symptoms of anxiety frequently occur concomitant to the development and persistence of inflammatory bowel disease (IBD) in patients. In the present study, we utilized an animal model of IBD, infection with Citrobacter rodentium, to determine whether the infection per se can drive anxiety-like behavior. Nine-week-old CF-1 male mice were challenged orally with either saline or C. rodentium. Early in the infective process (7-8 h later), mice were tested on a hole-board open field apparatus for anxiety-like behavior measurement. Immediately following behavioral testing, plasma samples were obtained for immune cytokine analysis and colons were excised for histological analysis. In additional animals, vagal ganglia were removed and processed for c-Fos protein detection. Challenge with C. rodentium significantly increased anxiety-like behavior as evidenced by avoidance of the center area and increased risk assessment behavior. Plasma levels of the cytokines IFN-gamma, TNF-alpha and IL-12 were not different. However vagal sensory ganglia from C. rodentium-treated animals evinced significantly more c-Fos protein-positive neurons, consistent with vagal afferent transmission of C. rodentium-related signals from gut to brain. Histological examination of the colon indicated a lack of overt inflammation at the 8 h post-challenge time point, indicating that the differences in behavior were unlikely to follow from inflammation-related stress. The results of the present study demonstrate that infection with C. rodentium can induce anxiety-like symptoms that are likely mediated via vagal sensory neurons.

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    • "Infections with certain pathogens are known to have neurobehavioral consequences , and inflammatory states affect behavior (Hornig, 2013). Autoimmune responses to gastrointestinal microorganisms , both pathogenic and commensal, increased anxiety (Trichuris muris in mice and Citrobacter rodentium) (Lyte et al., 2006;Bercik, 2010). Autism spectrum disorder (ASD) is a heterogeneous condition in children that affects the ability to communicate and socialize, and often presents with narrow interests and repetitive behaviors. "
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    • "It is well understood that via the axis that the brain can regulate gut activity (Cryan & O'Mahony 2011), but other works have focused on the reverse pathway and is indicating that the gut microbes can influence the brain. An investigation by Lyte et al. (2006) using mice demonstrated that the brain responds within hours to the introduction of a pathogen (C. rodentium) into the gut, long before manifestation of any infection-related symptoms. "
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    • "Therefore, these results must be interpreted with caution. The observed lack of effect of IAA treatment on hypothalamic c-fos expression seems to be in contrast to the many reports that describe an induction of c-fos expression in a variety of brain areas in response to a wide range of stressors, including restraint, swimming, audiogenic noise and immune challenge [60-63]. However, these stressors that induce c-fos expression are acute stressors. "
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