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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Association Learning / physiology
  • Avoidance Learning / physiology
  • Corticosterone / physiology
  • Early Growth Response Protein 1 / metabolism
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Male
  • Memory / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Neurologic Mutants
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinases / metabolism
  • Neurons / metabolism
  • PC12 Cells
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucocorticoid / metabolism*
  • Second Messenger Systems / physiology*
  • Signal Transduction / physiology*
  • Statistics, Nonparametric
  • Stress, Psychological / metabolism*
  • Synapsins / metabolism*


  • Early Growth Response Protein 1
  • Receptors, Glucocorticoid
  • Synapsins
  • Mitogen-Activated Protein Kinases
  • Corticosterone