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Glucocorticoids mediate stress-induced priming of microglial pro-inflammatory responses.
MedLine Citation:
PMID:  22041296     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 24h 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:
Matthew G Frank; Brittany M Thompson; Linda R Watkins; Steven F Maier
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-24
Journal Detail:
Title:  Brain, behavior, and immunity     Volume:  -     ISSN:  1090-2139     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-11-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8800478     Medline TA:  Brain Behav Immun     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Inc.
Affiliation:
Department of Psychology and Neuroscience, University of Colorado, Boulder, CO, USA.
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