Chronic exposure to exogenous glucocorticoids primes microglia to pro-inflammatory stimuli and induces NLRP3 mRNA in the hippocampus.
Chronic stress as well as chronic treatment with glucocorticoids (GCs) primes the neuroinflammatory response to a subsequent pro-inflammatory challenge. However, it remains unclear whether chronic GCs sensitize the response of key CNS immune substrates (i.e. microglia) to pro-inflammatory stimuli. In the present set of studies, male Sprague-Dawley rats underwent sham surgery or were adrenalectomized and then treated with varying concentrations of corticosterone (CORT; 0, 25, 50, and 75 μg/ml) administered in their drinking water. After 10 days of CORT exposure, whole hippocampus was collected and expression of glial activation markers measured or hippocampal microglia were isolated and challenged with LPS to probe for CORT-induced sensitization of pro-inflammatory responses. Chronic CORT exposure increased the gene expression of NLRP3, Iba-1, MHCII, and NF-κBIα in a concentration dependent manner. Chronic CORT (75 μg/ml) exposure potentiated the microglial proinflammatory response (TNFα, IL-1β, IL-6 and NLRP3) to LPS compared to the microglial response of sham surgery animals treated with vehicle. The present set of results demonstrate that chronic exposure to GCs primes microglia to pro-inflammatory stimuli and add to a growing body of evidence suggesting that a permissive function of GCs is that of an endogenous danger signal or alarmin.
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, Boulder, CO, USA. Electronic address: matt.frank@colorado.edu.
Matthew G
MG
Frank
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, Boulder, CO, USA.
Sarah A
SA
Hershman
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, Boulder, CO, USA.
Michael D
MD
Weber
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, Boulder, CO, USA.
Linda R
LR
Watkins
Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, Boulder, CO, USA.
Steven F
SF
Maier
D000818:Animals; D002352:Carrier Proteins; D016207:Cytokines / Q000378:metabolism; D004357:Drug Synergism; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D013315:Stress, Psychological / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D002352:Carrier Proteins; D016207:Cytokines; D005938:Glucocorticoids; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D018160:Receptors, Cytoplasmic and Nuclear
Glucocorticoids; Inflammasome; Microglia; Neuroinflammation; Priming; Stress