Rat area postrema microglial cells act as sensors for the toll-like receptor-4 agonist lipopolysaccharide

J Neuroimmunol. 2008 Nov 15;204(1-2):66-74. doi: 10.1016/j.jneuroim.2008.07.017.


The area postrema (AP) represents the sensory circumventricular organ lacking endothelial blood-brain barrier function in direct vicinity to the 4th cerebral ventricle. Administration of lipopolysaccharide (LPS), as opposed to muramyldipeptide (MDP) or fibroblast-stimulating lipopeptide-1 (FSL-1), caused fast transient rises in intracellular calcium concentrations in 10-12% of the microglial cells investigated in a primary microculture of the rat AP,with limited responses of neurons, astrocytes and oligodendrocytes. In addition, a marked release of the pro-inflammatory cytokines TNF-alpha and IL-6 was determined in LPS-treated AP microcultures. Pre-incubation of AP microcultures with LPS for 18 h suppressed LPS-induced calcium signaling and attenuated cytokine secretion. Evidently, the AP can act as a sensor for circulating LPS and has the capacity to develop endotoxin-tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Area Postrema / cytology*
  • Calcium / metabolism
  • Cells, Cultured
  • Female
  • Glial Fibrillary Acidic Protein / metabolism
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / pharmacology*
  • Male
  • Microglia / chemistry
  • Microglia / drug effects*
  • Microglia / immunology
  • Rats
  • Rats, Wistar
  • Time Factors
  • Toll-Like Receptor 4 / agonists*
  • Tumor Necrosis Factor-alpha / metabolism


  • Glial Fibrillary Acidic Protein
  • Interleukin-6
  • Lipopolysaccharides
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Calcium