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

Jean-Michel Revest (1) , Nadia Kaouane (1) , Françoise Rougé-Pont (1) , Anne Le Roux (1) , Monique Vallée (1) , Jacques Barik (1) , Aline Desmedt (1) , François Tronche (1) , Pier-Vincenzo Piazza (1) , Magali Mondin (1)

1 Aquitaine

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), 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 increases the expression of synapsin-Ia/Ib and second glucocorticoids driving MAPK activation increases 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; GEMS) through which stress and glucocorticoids enhance the memory of stress-related events and highlight the role of synapsin-Ia/Ib as molecular effector of the behavioral effects of stress.

Mots clés: glucocorticoids (GC); Glucocorticoid Receptors (GR); MAPK; Egr-1; synapsin-Ia/Ib; stress-related memory

Jean-Michel Revest, Nadia Kaouane, Françoise Rougé-Pont, Anne Le Roux, Monique Vallée, et al.. The enhancement of stress-related memory by glucocorticoids depends on synapsin-Ia/Ib. Molecular Psychiatry, 2010, ⟨10.1038/mp.2010.40⟩. ⟨hal-00523673⟩