Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium
Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium
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DOI：
10.1016/j.physbeh.2006.06.019
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发表时间：
2006-10-30
影响因子：
2.9
通讯作者：
Goehler, Lisa E.
中科院分区：
文献类型：
--
作者：
Lyte, Mark;Li, Wang;Goehler, Lisa E.
焦虑症状经常伴随着炎症性肠病(IBD)的发展和持续。在本研究中，我们使用了一种IBD的动物模型，即感染轮状柠檬酸杆菌，以确定感染本身是否会导致焦虑样行为。给9周龄的CF-1雄性小鼠灌胃生理盐水或轮状乳杆菌。在感染过程的早期(7-8小时后)，在孔板开放式设备上测试小鼠的焦虑样行为。行为测试结束后，立即采集血浆样本进行免疫细胞因子分析，切除结肠进行组织学分析。在其他动物中，取出迷走神经节并处理以进行c-Fos蛋白检测。通过回避中心区和增加风险评估行为的证据，用轮齿木霉攻击显著增加了焦虑样行为。血浆细胞因子干扰素-γ、肿瘤坏死因子-α和白介素12水平无明显差异。然而，迷走感觉神经节显示出更多的c-Fos蛋白阳性神经元，这与迷走神经传入信号从肠道到脑的传递是一致的。结肠的组织学检查表明，在攻击后8小时的时间点，没有明显的炎症反应，这表明行为上的差异不太可能源于炎症相关的应激。本研究的结果表明，感染轮状芽胞杆菌可引起焦虑样症状，这种症状可能通过迷走感觉神经元介导。(C)2006 Elsevier Inc.保留所有权利。
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. (c) 2006 Elsevier Inc. All rights reserved.