Microglia serve as a neuroimmune substrate for stress-induced potentiation of CNS pro-inflammatory cytokine responses

Brain Behav Immun. 2007 Jan;21(1):47-59. doi: 10.1016/j.bbi.2006.03.005. Epub 2006 May 2.


Prior exposure to a stressor can potentiate CNS pro-inflammatory immune responses to a peripheral immune challenge. However, the neuroimmune substrate(s) mediating this effect has not been determined. The present investigation examined whether microglia serve as this neuroimmune substrate given that microglia are the primary immune effector cell in the CNS. The effect of inescapable shock (IS) on glial activation (MHC II, CD11b, Iba-1, and GFAP) and regulatory markers (CD200) in vivo, and microglia pro-inflammatory responses (interleukin-1beta; IL-1beta) to lipopolysaccharide (LPS) ex vivo, were assessed in rat hippocampus. IS upregulated the microglia activation marker MHC II 24h post-IS, while the astroglia marker GFAP was unaffected. IS also downregulated the neuronal glycoprotein CD200, which functions to hold microglia in a quiescent state. Moreover, IS potentiated the pro-inflammatory response to LPS ex vivo 24h post-IS in isolated hippocampal microglia. Finally, the behavioral controllability of shock was manipulated and the effect of escapable (controllable) shock was comparable to the effect of IS on hippocampal microglia responses to LPS ex vivo. The present results suggest that stress can activate microglia, thereby sensitizing the pro-inflammatory reactivity of microglia to immunogenic stimuli.

MeSH terms

  • Animals
  • Gene Expression Profiling
  • Hippocampus / cytology
  • Hippocampus / immunology*
  • Histocompatibility Antigens / genetics
  • Histocompatibility Antigens / immunology
  • Histocompatibility Antigens / metabolism*
  • Immunohistochemistry
  • Interleukins / genetics
  • Interleukins / immunology
  • Interleukins / metabolism*
  • Lipopolysaccharides / immunology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Microglia / cytology
  • Microglia / immunology*
  • Microglia / metabolism
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Psychological / immunology*


  • Histocompatibility Antigens
  • Interleukins
  • Lipopolysaccharides
  • RNA, Messenger