期刊
MOLECULAR PSYCHIATRY
卷 19, 期 9, 页码 1001-1009出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2013.134
关键词
brain-derived neurotrophic factor; contextual fear memory; extracellular signal-regulated kinases 1/2 mitogen-activated protein kinase; glucocorticoids; tissue plasminogen activator; tropomyosin-related kinase B
资金
- INSERM
- Agence Nationale pour la Recherche (ANR)
- Federation Bordeaux Neurosciences (FBN)
- University Victor Segalen-Bordeaux2
- Conseil Regional d'Aquitaine
Activation of glucocorticoid receptors (GR) by glucocorticoid hormones (GC) enhances contextual fear memories through the activation of the Erk1/2(MAPK) signaling pathway. However, the molecular mechanism mediating this effect of GC remains unknown. Here we used complementary molecular and behavioral approaches in mice and rats and in genetically modified mice in which the GR was conditionally deleted (GR(NesCre)). We identified the tPA-BDNF-TrkB signaling pathway as the upstream molecular effectors of GR-mediated phosphorylation of Erk1/2(MAPK) responsible for the enhancement of contextual fear memory. These findings complete our knowledge of the molecular cascade through which GC enhance contextual fear memory and highlight the role of tPA-BDNFTrkB-Erk1/2(MAPK) signaling pathways as one of the core effectors of stress-related effects of GC.
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