Neural-immune interface in the rat area postrema.
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.
Goehler
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Program in Sensory and Systems Neuroscience, Department of Psychology and Neuroscience Graduate Program, University of Virginia, Charlottesville, VA 22904, USA. goehler@virginia.edu
Erisir
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Gaykema
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D000818:Animals; D000938:Antigen-Presenting Cells / Q000737:chemistry / Q000276:immunology / Q000648:ultrastructure; D031608:Area Postrema / Q000737:chemistry / Q000276:immunology* / Q000648:ultrastructure*; D005260:Female; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000276:immunology* / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley