Goehler L E, Erisir A, Gaykema R P A
Program in Sensory and Systems Neuroscience, Department of Psychology and Neuroscience Graduate Program, University of Virginia, Charlottesville, VA 22904, USA.
Neuroscience. 2006 Jul 21;140(4):1415-34. doi: 10.1016/j.neuroscience.2006.03.048. Epub 2006 May 2.
The area postrema functions as one interface between the immune system and the brain. Immune cells within the area postrema express immunoreactivity for the pro-inflammatory cytokine, interleukin-1beta following challenge with immune stimulants, including lipopolysaccharide (from bacterial cell walls). As a circumventricular organ, the area postrema accesses circulating immune-derived mediators, but also receives direct primary viscerosensory signals via the vagus nerve. Neurons in the area postrema contribute to central autonomic network neurocircuitry implicated in brain-mediated host defense responses. These experiments were directed toward clarifying relationships between immune cells and neurons in the area postrema, with a view toward potential mechanisms by which they may communicate. We used antisera directed toward markers indicating microglia (CR3/CD11b; OX-42), resident macrophages (CD163; ED-2), or dendritic cell-like phenotypes (major histocompability complex class II; OX-6), in area postrema sections from lipopolysaccharide-treated rats processed for light, laser scanning confocal, and electron microscopy. Lipopolysaccharide treatment induced interleukin-1beta-like immunoreactivity in immune cells that either associated with the vasculature (perivascular cells, a subtype of macrophage) or associated with neuronal elements (dendritic-like, and unknown phenotype). Electron microscopic analysis revealed that some immune cells, including interleukin-1beta-positive cells, evinced membrane apposition with neuronal elements, including dendrites and terminals, that could derive from inputs to the area postrema such as vagal sensory fibers, or intrinsic area postrema neurons. This arrangement provides an anatomical substrate by which immune cells could directly and specifically influence individual neurons in the area postrema, that may support the induction and/or maintenance of brain responses to inflammation.
最后区作为免疫系统与大脑之间的一个接口发挥作用。在用包括脂多糖（来自细菌细胞壁）在内的免疫刺激剂攻击后，最后区内的免疫细胞对促炎细胞因子白细胞介素-1β表现出免疫反应性。作为一个室周器官，最后区既能接触循环中的免疫衍生介质，也能通过迷走神经接收直接的初级内脏感觉信号。最后区的神经元参与了与脑介导的宿主防御反应相关的中枢自主神经网络神经回路。这些实验旨在阐明最后区免疫细胞与神经元之间的关系，以期了解它们可能进行通讯的潜在机制。我们使用针对指示小胶质细胞（CR3/CD11b；OX-42）、常驻巨噬细胞（CD163；ED-2）或树突状细胞样表型（主要组织相容性复合体II类；OX-6）的标志物的抗血清，对脂多糖处理的大鼠的最后区切片进行光镜、激光扫描共聚焦显微镜和电子显微镜观察。脂多糖处理诱导免疫细胞中白细胞介素-1β样免疫反应性，这些免疫细胞要么与脉管系统相关（血管周围细胞，巨噬细胞的一种亚型），要么与神经元成分相关（树突状样，以及未知表型）。电子显微镜分析显示，一些免疫细胞，包括白细胞介素-1β阳性细胞，与神经元成分（包括树突和终末）有膜附着，这些神经元成分可能来自诸如迷走感觉纤维或最后区固有神经元等传入最后区的信号。这种排列提供了一种解剖学基础，通过它免疫细胞可以直接且特异性地影响最后区的单个神经元，这可能支持大脑对炎症反应的诱导和/或维持。
