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

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

Author Munhoz, Carolina Demarchi Google Scholar
Lepsch, Lucilia B. Google Scholar
Kawamoto, Elisa Mitiko Google Scholar
Malta, Marília Brinati Google Scholar
Lima, Larissa de Sá Google Scholar
Avellar, Maria Cristina Werneck Autor UNIFESP Google Scholar
Sapolsky, Robert M. Google Scholar
Scavone, Cristoforo Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Stanford Univ
Abstract 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.
Keywords glucocorticoids
chronic stress
NF-kappa B
LPS
NMDA
brain
Language English
Date 2006-04-05
Published in Journal of Neuroscience. Washington: Soc Neuroscience, v. 26, n. 14, p. 3813-3820, 2006.
ISSN 0270-6474 (Sherpa/Romeo, impact factor)
Publisher Soc Neuroscience
Extent 3813-3820
Origin http://dx.doi.org/10.1523/JNEUROSCI.4398-05.2006
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000236552400023
URI http://repositorio.unifesp.br/handle/11600/28843

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