Article

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

ABSTRACT

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.

Download full-text

Full-text

Available from: Lisa E Goehler
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: This review describes current understandings about the nature of the very low birth weight infant (VLBW) gut microbiome. VLBW infants often experience disruptive pregnancies and births, and prenatal factors can influence the maturity of the gut and immune system, and disturb microbial balance and succession. Many VLBWs experience rapid vaginal or Caesarean births. After birth these infants often have delays in enteral feeding, and many receive little or no mother's own milk. Furthermore the stressors of neonatal life in the hospital environment, common use of antibiotics, invasive procedures and maternal separation can contribute to dysbiosis. These infants experience gastrointestinal dysfunction, sepsis, transfusions, necrotizing enterocolitis, oxygen toxicity, and other pathophysiological consditions that affect the normal microbiota. The skin is susceptible to dysbiosis, due to its fragility and contact with NICU organisms. Dysbiosis in early life may resolve but little is known about the timing of the development of the signature gut microbiome in VLBWs. Dysbiosis has been associated with a number of physical and behavioral problems, including autism spectrum disorders, allergy and asthma, gastrointestinal disease, obesity, depression, and anxiety. Dysbiosis may be prevented or ameliorated in part by prenatal care, breast milk feeding, skin to skin contact, use of antibiotics only when necessary, and vigilance during infancy and early childhood. Birth Defects Research (Part C), 2015. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Dec 2015 · Birth Defects Research Part C Embryo Today Reviews
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The human body is home to trillions of microorganisms which are increasingly being shown to have significant effects on a variety of disease states. Evidence exists that a bidirectional communication is taking place between us and our microbiome co-habitants, and that this dialogue is capable of influencing our health in a variety of ways. This review considers how host hormonal signals shape the microbiome, and what in return the microbiome residents may be signalling to their hosts.
    Preview · Article · Mar 2015 · Journal of Endocrinology
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Human and animals studies support the idea that there is a gender-related co-morbidity of pain-related and inflammatory gastrointestinal (GI) diseases with psychological disorders. This co-morbidity is the evidence for the existence of GI-brain axis which consists of immune (cytokines), neural (vagus nerve) and neuroendocrine (HPA axis) pathways. Psychological stress causes disturbances in GI physiology, such as altered GI barrier function, changes in motility and secretion, development of visceral hypersensitivity, and dysfunction of inflammatory responses. Whether GI inflammation would exert impact on psychological behavior is not well established. We examined the effect of experimental gastritis on anxiety- and depression-like behaviors in male and female Sprague-Dawley rats, and evaluated potential mechanisms of action. Gastritis was induced by adding 0.1% (w/v) iodoacetamide (IAA) to the sterile drinking water for 7 days. Sucrose preference test assessed the depression-like behavior, open field test and elevated plus maze evaluated the anxiety-like behavior. IAA treatment induced gastric inflammation in rats of either gender. No behavioral abnormality or dysfunction of GI-brain axis was observed in male rats with IAA-induced gastritis. Anxiety- and depression-like behaviors were apparent and the HPA axis was hyperactive in female rats with IAA-induced gastritis. Our results show that gastric inflammation leads to anxiety- and depression-like behaviors in female but not male rats via the neuroendocrine (HPA axis) pathway, suggesting that the GI inflammation can impair normal brain function and induce changes in psychological behavior in a gender-related manner through the GI-to-brain signaling.
    Full-text · Article · Dec 2013 · Behavioral and Brain Functions
Show more