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Mol Psychiatry. 2014 Sep;19(9):1001-9. doi: 10.1038/mp.2013.134. Epub 2013 Oct 15.

BDNF-TrkB signaling through Erk1/2 MAPK phosphorylation mediates the enhancement of fear memory induced by glucocorticoids.

Author information

1
1] INSERM U862, Neurocentre Magendie, Pathophysiology of Addiction, Bordeaux, France [2] Pathophysiology of Neuronal Plasticity, Université de Bordeaux, Bordeaux, France.
2
1] Pathophysiology of Neuronal Plasticity, Université de Bordeaux, Bordeaux, France [2] INSERM U862, Neurocentre Magendie, Pathophysiology of Declarative Memory, Bordeaux, France.
3
CNRS UMR7224, UPMC Université Pierre et Marie Curie, Molecular Genetics, Neurophysiology and Behavior, Paris, France.

Abstract

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-BDNF-TrkB-Erk1/2(MAPK) signaling pathways as one of the core effectors of stress-related effects of GC.

PMID:
24126929
PMCID:
PMC4195976
DOI:
10.1038/mp.2013.134
[Indexed for MEDLINE]
Free PMC Article

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