Divergent effects of repeated restraint versus chronic variable stress on prefrontal cortical immune status after LPS injection

Brain Behav Immun. 2016 Oct;57:263-270. doi: 10.1016/j.bbi.2016.05.004. Epub 2016 May 10.


Previous work from our group has shown that chronic homotypic stress (repeated restraint - RR) increases microglial morphological activation in the prefrontal cortex (PFC), while chronic heterotypic stress (chronic variable stress - CVS) produces no such effect. Therefore, we hypothesized that stressor modality would also determine the susceptibility of the PFC to a subsequent inflammatory stimulus (low dose lipopolysaccharide (LPS)). We found that RR, but not CVS, increased Iba-1 soma size in the PFC after LPS injection, consistent with microglial activation. In contrast, CVS decreased gene expression of proinflammatory cytokines and Iba-1 in the PFC under baseline conditions, which were not further affected by LPS. Thus, RR appears to promote microglial responses to LPS, whereas CVS is largely immunosuppressive. The results suggest that neuroimmune changes caused by CVS may to some extent protect the PFC from subsequent inflammatory stimuli. These data suggest that modality and/or intensity of stressful experiences will be a major determinant of central inflammation and its effect on prefrontal cortex-mediated functions.

Keywords: Chronic stress; Cytokines; LPS; Microglia; Prefrontal cortex.

MeSH terms

  • Animals
  • Calcium-Binding Proteins / metabolism
  • Cytokines / metabolism*
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / pharmacology*
  • Male
  • Microfilament Proteins / metabolism
  • Microglia / immunology*
  • Prefrontal Cortex / immunology*
  • Prefrontal Cortex / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Psychological / classification
  • Stress, Psychological / immunology*
  • Stress, Psychological / metabolism


  • Aif1 protein, rat
  • Calcium-Binding Proteins
  • Cytokines
  • Lipopolysaccharides
  • Microfilament Proteins