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Mol Psychiatry. 2010 Dec;15(12):1125, 1140-51. doi: 10.1038/mp.2010.40. Epub 2010 Apr 6.

The enhancement of stress-related memory by glucocorticoids depends on synapsin-Ia/Ib.

Author information

1
INSERM U862, Neurocentre Magendie, Pathophysiology of Addiction group, Bordeaux, France. jean-michel.revest@inserm.fr

Abstract

The activation of glucocorticoid receptors (GR) by glucocorticoids increases stress-related memory through the activation of the MAPK signaling pathway and the downstream transcription factor Egr-1. Here, using converging in vitro and in vivo approaches, respectively, GR-expressing cell lines, culture of hippocampal neurons, and GR genetically modified mice (GR(NesCre)), we identified synapsin-Ia/Ib as one of the effectors of the glucocorticoid signaling cascade. Stress and glucocorticoid-induced activation of the GR modulate synapsin-Ia/Ib through two complementary mechanisms. First, glucocorticoids driving Egr-1 expression increase the expression of synapsin-Ia/Ib, and second, glucocorticoids driving MAPK activation increase its phosphorylation. Finally, we showed that blocking fucosylation of synapsin-Ia/Ib in the hippocampus inhibits its expression and prevents the glucocorticoid-mediated increase in stress-related memory. In conclusion, our data provide a complete molecular pathway (GR/Egr-1/MAPK/Syn-Ia/Ib) through which stress and glucocorticoids enhance the memory of stress-related events and highlight the function of synapsin-Ia/Ib as molecular effector of the behavioral effects of stress.

PMID:
20368707
PMCID:
PMC2990189
DOI:
10.1038/mp.2010.40
[Indexed for MEDLINE]
Free PMC Article

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