The MAPK pathway and Egr-1 mediate stress-related behavioral effects of glucocorticoids.
Nat Neurosci
; 8(5): 664-72, 2005 May.
Article
em En
| MEDLINE
| ID: mdl-15834420
ABSTRACT
Many of the behavioral consequences of stress are mediated by the activation of the glucocorticoid receptor by stress-induced high levels of glucocorticoid hormones. To explore the molecular mechanisms of these effects, we combined in vivo and in vitro approaches. We analyzed mice carrying a brain-specific mutation (GR(NesCre)) in the glucocorticoid receptor gene (GR, also called Nr3c1) and cell lines that either express endogenous glucocorticoid receptor or carry a constitutively active form of the receptor (DeltaGR) that can be transiently induced. In the hippocampus of the wild-type [corrected] mice after stress, as well as in the cell lines, activation of glucocorticoid receptors greatly increased the expression and enzymatic activity of proteins in the MAPK signaling pathway and led to an increase in the levels of both Egr-1 mRNA and protein. In parallel, inhibition of the MAPK pathway within the hippocampus abolished the increase in contextual fear conditioning induced by glucocorticoids. The present results provide a molecular mechanism for the stress-related effects of glucocorticoids on fear memories.
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Base de dados:
MEDLINE
Assunto principal:
Estresse Fisiológico
/
Fatores de Transcrição
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Receptores de Glucocorticoides
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Proteínas Imediatamente Precoces
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Sistema de Sinalização das MAP Quinases
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Proteínas de Ligação a DNA
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Glucocorticoides
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Hipocampo
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article