Gaykema Ronald P A, Goehler Lisa E, Lyte Mark
Department of Psychology and Neuroscience Graduate Program, University of Virginia, Charlottesville, VA 22904, USA.
Brain Behav Immun. 2004 May;18(3):238-45. doi: 10.1016/j.bbi.2003.08.002.
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.
如食源性病原体空肠弯曲菌所示，感染细菌性病原体可在啮齿动物中诱发焦虑样行为增加，而无其他明显的疾病行为或生理症状。这一观察结果表明大脑有感知并应对此类感染的能力。我们检验了以下假设：革兰氏阴性菌空肠弯曲菌引起的肠道感染会导致处理胃肠感觉信息的某些脑区被激活。与用生理盐水处理的对照组相比，在经口接种活空肠弯曲菌的小鼠大脑中评估了作为神经元激活标志物的c-Fos蛋白的诱导情况。在肠道定植后，空肠弯曲菌在口服攻击后一天和两天均激活了脑干中的内脏感觉核（孤束核和外侧臂旁核）。此外，第二天下丘脑室旁核中的c-Fos表达增加。这种神经反应发生在没有可测量的全身免疫激活的情况下，因为肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6的血清水平无法检测到和/或未发生变化。这些发现支持了这样一种观点，即肠道中空肠弯曲菌感染的信息确实会传递到大脑中的内脏感觉结构。观察到的大脑反应可能导致感染后行为的变化。
