Glucocorticoids Exacerbate Lipopolysaccharide-Induced Signaling in the Frontal Cortex and Hippocampus in a Dose-Dependent Manner

Autor(es)

Munhoz, Carolina Demarchi ^{[1, 2]} ; Sorrells, Shawn F. ^[2] ; Caso, Javier R. ^[2] ; Scavone, Cristoforo ^[1] ; Sapolsky, Robert M. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Pharmacol, Inst Biomed Sci, BR-05508900 Sao Paulo - Brazil

^[2] Stanford Univ, Dept Biol Sci, Stanford, CA 94305 - USA

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF NEUROSCIENCE; v. 30, n. 41, p. 13690-13698, OCT 13 2010.
• Citações Web of Science: 77

Resumo

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-kappa B (nuclear factor kappa B), 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-kappa B, 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. (AU)

• Processo FAPESP: 04/11041-0 - Participacao das map kinases, proteinas de choque termico e da via de apoptose nos efeitos adversos dos glicocorticoides no sistema nervoso central.
• Beneficiário: Cristoforo Scavone
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 04/11042-7 - Participacao das map kinases, proteinas de choque termico e da via de apoptose nos efeitos adversos dos glicocorticoides no sistema nervoso central.
• Beneficiário: Carolina Demarchi Munhoz
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 02/02298-2 - Estresse e a sinalizacao intracelular na inflamacao desencadeada pelo lps no sistema nervoso central: participacao dos glicocorticoides e da via glutamato-no na modulacao do fator de transcricao nf-kb.
• Beneficiário: Cristoforo Scavone
• Modalidade de apoio: Auxílio à Pesquisa - Regular