Portal de Periódicos da CAPES

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

2010; Springer Nature; Volume: 15; Issue: 12 Linguagem: Inglês

10.1038/mp.2010.40

1476-5578

J-M Revest, Nadia Kaouane, Magali Mondin, A Le Roux, Françoise Rougé‐Pont, Monique Vallée, Jacques Barik, François Tronche, Aline Desmedt, Pier‐Vincenzo Piazza,

Neuroscience and Neuropharmacology Research

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 (GRNesCre), 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.