Chronic unpredictable stress exacerbates lipopolysaccharide-induced activation of nuclear factor-kappa B in the frontal cortex and hippocampus via glucocorticoid secretion

Although the anti-inflammatory actions of glucocorticoids (GCs) are well established in the periphery, these stress hormones can increase inflammation under some circumstances in the brain. the transcription factor nuclear factor-kappa B (NF-kappa B), which is inhibited by GCs, regulates numerous ge...

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Bibliographic Details
Authors: Munhoz, Carolina Demarchi, Lepsch, Lucilia Brochado, Kawamoto, Elisa Mitiko, Malta, Marília Brinati, Lima, Larissa de Sá, Avellar, Maria Christina Werneck [UNIFESP], Sapolsky, Robert M., Scavone, Cristoforo
Format: article
Status:Published version
Publication Date:2006
Country:Brasil
Institution:Universidade Federal de São Paulo (UNIFESP)
Repository:Repositório Institucional da UNIFESP
Language:English
OAI Identifier:oai:repositorio.unifesp.br:11600/28843
Online Access:https://dx.doi.org/10.1523/JNEUROSCI.4398-05.2006
https://repositorio.unifesp.br/handle/11600/28843
Access Level:Open access
Keyword:Glucocorticoids
Chronic stress
NF-kappa B
LPS
NMDA
Brain
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Summary:Although the anti-inflammatory actions of glucocorticoids (GCs) are well established in the periphery, these stress hormones can increase inflammation under some circumstances in the brain. the transcription factor nuclear factor-kappa B (NF-kappa B), which is inhibited by GCs, regulates numerous genes central to inflammation. in this study, the effects of stress, GCs, and NMDA receptors on lipopolysaccharide (LPS)-induced activation of NF-kappa B in the brain were investigated. One day after chronic unpredictable stress (CUS), nonstressed and CUS rats were treated with saline or LPS and killed 2 h later. CUS potentiated the increase in LPS-induced activation of NF-kappa B in frontal cortex and hippocampus but not in the hypothalamus. This stress effect was blocked by pretreatment of rats with RU-486, an antagonist of the GC receptor. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate], an NMDA receptor antagonist, also reduced the effect of LPS in all three brain regions. However, the combined antagonism of both GC and NMDA receptors produced no further reduction in NF-kappa B activation when compared with the effect of each treatment alone. Our results indicate that stress, via GC secretion, can increase LPS-induced NF-kappa B activation in the frontal cortex and hippocampus, agreeing with a growing literature demonstrating proinflammatory effects of GCs.

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