Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells
Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells
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DOI：
10.1172/jci78361
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发表时间：
2015-02-01
影响因子：
15.9
通讯作者：
Liddle, Rodger A.
中科院分区：
文献类型：
--
作者：
Bohorquez, Diego V.;Shahid, Rafiq A.;Liddle, Rodger A.
饱腹感和其他核心生理功能由肠道表面产生的感觉信号调节。管腔内的营养物质和细菌刺激上皮生物传感器，称为肠内分泌细胞。尽管是电兴奋的，肠内分泌细胞通常被认为是通过激素分泌间接与神经沟通，而不是通过直接的细胞-神经接触。然而，我们最近在肠内分泌细胞中发现了一个我们命名为neuropod的细胞质过程。在这里，我们确定，neuropod提供了一个直接的肠内分泌细胞和神经元支配小肠和结肠之间的联系。使用细胞特异性转基因小鼠研究神经回路，我们发现肠内分泌细胞具有神经传递的必要元素，包括编码前，后和transstynaptic蛋白的基因的表达。通过将单个肠内分泌细胞与感觉神经元共培养，在体外重建神经上皮回路。我们使用单突触狂犬病病毒来定义回路在体内的功能连接，并确定将这种嗜神经病毒递送到结肠腔中导致粘膜神经通过肠内分泌细胞感染。这种神经上皮回路既可以作为食物和肠道微生物与神经系统相互作用的感觉管道，也可以作为病毒进入肠道和中枢神经系统的门户。
Satiety and other core physiological functions are modulated by sensory signals arising from the surface of the gut. Luminal nutrients and bacteria stimulate epithelial biosensors called enteroendocrine cells. Despite being electrically excitable, enteroendocrine cells are generally thought to communicate indirectly with nerves through hormone secretion and not through direct cell-nerve contact. However, we recently uncovered in intestinal enteroendocrine cells a cytoplasmic process that we named neuropod. Here, we determined that neuropods provide a direct connection between enteroendocrine cells and neurons innervating the small intestine and colon. Using cell-specific transgenic mice to study neural circuits,we found that enteroendocrine cells have the necessary elements for neurotransmission, including expression of genes that encode pre-, post-, and transstynaptic proteins. This neuroepithelial circuit was reconstituted in vitro by coculturing single enteroendocrine cells with sensory neurons. We used a monosynaptic rabies virus to define the circuit's functional connectivity in vivo and determined that delivery of this neurotropic virus into the colon lumen resulted in the infection of mucosal nerves through enteroendocrine cells. This neuroepithelial circuit can serve as both a sensory conduit for food and gut microbes to interact with the nervous system and a portal for viruses to enter the enteric and central nervous systems.