Brain response to cecal infection with Campylobacter jejuni: analysis with Fos immunohistochemistry.
Infections with bacterial pathogens can induce increased anxiety-like behaviors in rodents without otherwise noticeable behavioral or physiological symptoms of sickness, as shown with the food-borne pathogen Campylobacter jejuni. This observation implicates the ability of the brain to sense, and respond to, such an infection. We tested our hypothesis that intestinal infection with the gram-negative bacterium C. jejuni leads to activation of certain brain regions that process gastro-intestinal sensory information. The induction of c-Fos protein as a marker for neuronal activation was assessed in the brains of mice inoculated orally with live C. jejuni, as compared to saline-treated controls. Upon colonization of the intestines, C. jejuni activated visceral sensory nuclei in the brainstem (the nucleus of the solitary tract and the lateral parabrachial nucleus) both one and two days after the oral challenge. In addition, increased c-Fos expression occurred in the hypothalamic paraventricular nucleus on the second day. This neural response occurred in the absence of measurable systemic immune activation, as serum levels of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 were undetectable and/or unchanged. These findings support the notion that information about infection with C. jejuni in the gut is indeed relayed to the visceral sensory structures in the brain. The brain responses observed could contribute to changes in behavior observed after infection.
Gaykema
Ronald P A
RP
Department of Psychology and Neuroscience Graduate Program, University of Virginia, Charlottesville, VA 22904, USA. gaykema@virginia.edu
Goehler
Lisa E
LE
Lyte
Mark
M
D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000276:immunology* / Q000378:metabolism; D002169:Campylobacter Infections / Q000276:immunology*; D016123:Campylobacter jejuni / Q000276:immunology*; D002432:Cecum / Q000276:immunology / Q000382:microbiology*; D016207:Cytokines / Q000097:blood; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015213:Neuroimmunomodulation / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000276:immunology / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D017552:Solitary Nucleus / Q000276:immunology / Q000378:metabolism; D013681:Tegmentum Mesencephali / Q000276:immunology / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D016760:Proto-Oncogene Proteins c-fos