TY - JOUR T1 - Chronic Unpredictable Stress Exacerbates Lipopolysaccharide-Induced Activation of Nuclear Factor-κB in the Frontal Cortex and Hippocampus via Glucocorticoid Secretion JF - The Journal of Neuroscience JO - J. Neurosci. SP - 3813 LP - 3820 DO - 10.1523/JNEUROSCI.4398-05.2006 VL - 26 IS - 14 AU - Carolina Demarchi Munhoz AU - Lucilia B. Lepsch AU - Elisa Mitiko Kawamoto AU - Marília Brinati Malta AU - Larissa de Sá Lima AU - Maria Christina Werneck Avellar AU - Robert M. Sapolsky AU - Cristoforo Scavone Y1 - 2006/04/05 UR - http://www.jneurosci.org/content/26/14/3813.abstract N2 - 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-κB (NF-κB), 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-κB 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-κB 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-κB activation when compared with the effect of each treatment alone. Our results indicate that stress, via GC secretion, can increase LPS-induced NF-κB activation in the frontal cortex and hippocampus, agreeing with a growing literature demonstrating proinflammatory effects of GCs. ER -