The enhancement of stress-related memory by glucocorticoids depends on synapsin-Ia/Ib.
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.
Revest
J-M
JM
INSERM U862, Neurocentre Magendie, Pathophysiology of Addiction group, Bordeaux, France. jean-michel.revest@inserm.fr
Kaouane
N
N
Mondin
M
M
Le Roux
A
A
Rougé-Pont
F
F
Vallée
M
M
Barik
J
J
Tronche
F
F
Desmedt
A
A
Piazza
P V
PV
D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000502:physiology; D001362:Avoidance Learning / Q000502:physiology; D003345:Corticosterone / Q000502:physiology; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015290:Second Messenger Systems / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000378:metabolism*; D016704:Synapsins / Q000378:metabolism*
D051766:Early Growth Response Protein 1; D011965:Receptors, Glucocorticoid; D016704:Synapsins; D020928:Mitogen-Activated Protein Kinases; D003345:Corticosterone