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首页> 外文期刊>The European Journal of Neuroscience >CXCR4 receptors in the dorsal medulla: implications for autonomic dysfunction.
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CXCR4 receptors in the dorsal medulla: implications for autonomic dysfunction.

机译：背髓中的CXCR4受体：对植物神经功能障碍的影响。

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The chemokine receptor, CXCR4, plays an essential role in guiding neural development of the CNS. Its natural agonist, CXCL12 [or stromal cell-derived factor-1 (SDF-1)], normally is derived from stromal cells, but is also produced by damaged and virus-infected neurons and glia. Pathologically, this receptor is critical to the proliferation of the HIV virus and initiation of metastatic cell growth in the brain. Anorexia, nausea and failed autonomic regulation of gastrointestinal (GI) function cause morbidity and contribute to the mortality associated with these disease states. Our previous work on the peripheral cytokine, tumor necrosis factor-alpha, demonstrated that similar morbidity factors involving GI dysfunction are attributable to agonist action on neural circuit elements of the dorsal vagal complex (DVC) of the hindbrain. The DVC includes vagal afferent terminations in the solitary nucleus, neurons in the solitary nucleus (NST) and area postrema, and visceral efferent motor neurons in the dorsal motor nucleus (DMN) that are responsible for the neural regulation of digestive functions from the oral cavity to the transverse colon. Immunohistochemical techniques demonstrate a dense concentration of CXCR4 receptors on neurons throughout the DVC and the hypoglossal nucleus. CXCR4-immunoreactivity is also intense on microglia within the DVC, though not on the astrocytes. Physiological studies show that nanoinjection of SDF-1 into the DVC produces a significant reduction in gastric motility in parallel with an elevation in the numbers of cFOS-activated neurons in the NST and DMN. These results suggest that this chemokine receptor may contribute to autonomically mediated pathophysiological events associated with CNS metastasis and infection.
机译：趋化因子受体CXCR4在指导中枢神经系统的神经发育中起重要作用。它的天然激动剂CXCL12 [或基质细胞衍生因子1（SDF-1）]通常来自基质细胞，但也由受损和感染病毒的神经元和神经胶质细胞产生。在病理学上，该受体对于HIV病毒的扩散和大脑中转移性细胞生长的启动至关重要。厌食，恶心和胃肠道（GI）功能的自主神经调节失败会导致发病，并导致与这些疾病状态相关的死亡率。我们先前对外周细胞因子肿瘤坏死因子-α的研究表明，涉及胃肠功能障碍的相似发病因素可归因于对后脑背迷走神经复合体（DVC）神经回路元件的激动作用。 DVC包括孤立核中的迷走神经传入终端，孤立核（NST）和视网膜后区域中的神经元，以及背运动核（DMN）中的内脏传入运动神经元，它们负责口腔消化功能的神经调节横结肠。免疫组织化学技术表明，在整个DVC和舌下神经核中，神经元上均富含CXCR4受体。 CXCR4免疫反应性在DVC内的小胶质细胞上也很强，尽管在星形胶质细胞上却没有。生理研究表明，向DVC纳米注射SDF-1会导致胃动力显着降低，同时NST和DMN中cFOS激活的神经元数量增加。这些结果表明该趋化因子受体可能有助于与CNS转移和感染相关的自主介导的病理生理事件。

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