Campylobacter jejuni infection increases anxiety-like behavior in the holeboard:: Possible anatomical substrates for viscerosensory modulation of exploratory behavior
Campylobacter jejuni infection increases anxiety-like behavior in the holeboard:: Possible anatomical substrates for viscerosensory modulation of exploratory behavior
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DOI：
10.1016/j.bbi.2007.08.009
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发表时间：
2008-03-01
影响因子：
15.1
通讯作者：
Gaykema, Ronald P. A.
中科院分区：
文献类型：
--
作者：
Goehler, Lisa E.;Park, Su Mi;Gaykema, Ronald P. A.
胃肠道中某些细菌的存在会影响行为和大脑功能。例如，用活空肠弯曲杆菌（C jejuni）（一种常见的食源性病原体）进行挑战，会减少对十字迷宫张开臂的探索，这与焦虑样行为一致，并可能通过迷走神经通路激活与自主功能相关的大脑区域。然而，迄今为止，人们对免疫感觉信号与介导行为状态变化的大脑基质的界面知之甚少。为了解决这个问题，我们用空肠弯曲菌或盐水挑战小鼠，7-8小时后使用开放孔板评估焦虑样行为，并使用免疫组织化学检测蛋白质c-Fos作为大脑中的激活标记。与盐水处理的对照相比，空肠弯曲菌处理与对孔板中心区域的回避增加相关。暴露于孔板中会诱导先前与焦虑样行为有关的多个大脑区域的激活，包括侧隔膜（LS）、室旁核（PVN）和下丘脑背内侧核（DMH）、杏仁核基底外侧核和中央核（BLA、CEA）、终纹床核（BST）和导水管周围灰质（PAG）， 与家庭笼控制相比。如先前报道，在空肠弯曲菌处理的动物中，c-Fos 诱导也发生在自主神经区域。 PVN、BLA、BST 的部分、内侧前额叶 (mPFC) 和前扣带回对空肠弯曲菌治疗和孔板都有反应，表明这些区域在观察到的增强的焦虑样行为中发挥作用。在盐水处理的动物中，焦虑样行为是通过 CEA 和 BLA 的激活来预测的，而在空肠弯曲菌处理的动物中，BST 中的 c-Fos 表达可以预测焦虑样行为的程度。这些发现表明 PVN、杏仁核和 BST 是胃肠道致病性挑战和介导对压力的行为反应的大脑区域之间的接口，并强化了这些核作为内脏感觉刺激可以影响行为的解剖学基础。 (c) 2007 Elsevier Inc. 保留所有权利。
The presence of certain bacteria in the gastrointestinal tract influences behavior and brain function. For example, challenge with live Campylobacter jejuni (C jejuni), a common food-born pathogen, reduces exploration of open arms of the plus maze, consistent with anxiety-like behavior, and activates brain regions associated with autonomic function, likely via a vagal pathway. As yet, however, little is known regarding the interface of immune sensory signals with brain substrates that mediate changes in behavioral states. To address this issue, we challenged mice with either C jejuni or saline, and 7-8 h later assessed anxiety-like behavior using the open holeboard, and used immunohistochemical detection of the protein c-Fos as an activation marker in the brain. C jejuni treatment was associated with increased avoidance of the center regions of the holeboard, compared to saline-treated controls. Exposure to the holeboard induced activation in multiple brain regions previously implicated in anxiety-like behavior, including the lateral septum (LS), paraventricular (PVN) and dorsomedial hypothalamic nuclei (DMH), basolateral and central nuclei of the amygdala (BLA, CEA), bed nucleus of the stria terminalis (BST) and periaquiductal grey (PAG), compared to homecage controls. In C jejuni-treated animals c-Fos induction also occurred in autonomic regions, as previously reported. The PVN, BLA, parts of the BST, medial prefrontal (mPFC) and anterior cingulate responded to both C jejuni treatment and the holeboard, suggesting a role for these regions in the enhanced anxiety-like behavior observed. In saline-treated animals, anxiety-like behavior was predicted by activation in the CEA and BLA, whereas in C jejuni-treated animals, c-Fos expression in the BST predicted the degree of anxiety-like behavior. These findings implicate the PVN, amygdala and BST as interfaces between gastrointestinal pathogenic challenge and brain regions that mediate behavioral responses to stress, and reinforce these nuclei as anatomical substrates by which viscerosensory stimuli can influence behavior. (c) 2007 Elsevier Inc. All rights reserved.