title: Glucocorticoids mediate stress-induced priming of microglial pro-inflammatory responses.
abstract: Acute and chronic stress sensitizes or "primes" the neuroinflammatory response to a subsequent pro-inflammatory challenge. While prior evidence shows that glucocorticoids (GCs) play a pivotal role in stress-induced potentiation of neuroinflammatory responses, it remains unclear whether stress-induced GCs sensitize the response of key CNS immune substrates (i.e. microglia) to pro-inflammatory stimuli. An ex vivo approach was used to address this question. Here, stress-induced GC signaling was manipulated in vivo and hippocampal microglia challenged with the pro-inflammatory stimulus LPS ex vivo. Male Sprague-Dawley rats were either pretreated in vivo with the GC receptor antagonist RU486 or adrenalectomized (ADX). Animals were then exposed to an acute stressor (inescapable tailshock; IS) and 24 h later hippocampal microglia were isolated and challenged with LPS to probe for stress-induced sensitization of pro-inflammatory responses. Prior exposure to IS resulted in a potentiated pro-inflammatory cytokine response (e.g. IL-1β gene expression) to LPS in isolated microglia. Treatment in vivo with RU486 and ADX inhibited or completely blocked this IS-induced sensitization of the microglial pro-inflammatory response. The present results suggest that stress-induced GCs function to sensitize the microglial pro-inflammatory response (IL-1β, IL-6, NFκBIα) to immunologic challenges.
authors: Department of Psychology and Neuroscience, University of Colorado, Boulder, CO 80309-0345, USA. matt.frank@colorado.edu
authors: Matthew G
authors: MG
authors: Frank
authors: Brittany M
authors: BM
authors: Thompson
authors: Linda R
authors: LR
authors: Watkins
authors: Steven F
authors: SF
authors: Maier
mesh_terms: D000315:Adrenalectomy; D000818:Animals; D005938:Glucocorticoids / Q000097:blood / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D053583:Interleukin-1beta / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D013315:Stress, Psychological / Q000150:complications* / Q000276:immunology / Q000503:physiopathology
chemical_list: D005938:Glucocorticoids; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011965:Receptors, Glucocorticoid; D015735:Mifepristone