RT Journal Article
SR Electronic
T1 Glucocorticoids Exacerbate Lipopolysaccharide-Induced Signaling in the Frontal Cortex and Hippocampus in a Dose-Dependent Manner
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 13690
OP 13698
DO 10.1523/JNEUROSCI.0303-09.2010
VO 30
IS 41
A1 Carolina Demarchi Munhoz
A1 Shawn F. Sorrells
A1 Javier R. Caso
A1 Cristoforo Scavone
A1 Robert M. Sapolsky
YR 2010
UL http://www.jneurosci.org/content/30/41/13690.abstract
AB Although the anti-inflammatory actions of glucocorticoids (GCs) are well established, evidence has accumulated showing that proinflammatory GC effects can occur in the brain, in a poorly understood manner. Using electrophoretic mobility shift assay, real-time PCR, and immunoblotting, we investigated the ability of varying concentrations of corticosterone (CORT, the GC of rats) to modulate lipopolysaccharide (LPS)-induced activation of NF-κB (nuclear factor κB), expression of anti- and proinflammatory factors and of the MAP (mitogen-activated protein) kinase family [ERK (extracellular signal-regulated kinase), p38, and JNK/SAPK (c-Jun N-terminal protein kinase/stress-activated protein kinase)], and AKT. In the frontal cortex, elevated CORT levels were proinflammatory, exacerbating LPS effects on NF-κB, MAP kinases, and proinflammatory gene expression. Milder proinflammatory GCs effects occurred in the hippocampus. In the absence of LPS, elevated CORT levels increased basal activation of ERK1/2, p38, SAPK/JNK, and AKT in both regions. These findings suggest that GCs do not uniformly suppress neuroinflammation and can even enhance it at multiple levels in the pathway linking LPS exposure to inflammation.