Glucocorticoid receptors are localized to dendritic spines and influence local actin signaling

Mol Neurobiol. 2012 Oct;46(2):304-15. doi: 10.1007/s12035-012-8288-3. Epub 2012 Jun 21.


Glucocorticoids affect learning and memory but the cellular mechanisms involved are poorly understood. The present studies tested if the stress-responsive glucocorticoid receptor (GR) is present and regulated within dendritic spines, and influences local signaling to the actin cytoskeleton. In hippocampal field CA1, 13 % of synapses contained GR-immunoreactivity. Three-dimensional reconstructions of CA1 dendrites showed that GR aggregates are present in both spine heads and necks. Consonant with evidence that GRα mRNA associates with the translation regulator Fragile X Mental Retardation Protein (FMRP), spine GR levels were rapidly increased by group 1 mGluR activation and reduced in mice lacking FMRP. Treatment of cultured hippocampal slices with the GR agonist dexamethasone rapidly (15-30 min) increased total levels of phosphorylated (p) Cofilin and extracellular signal-regulated kinase (ERK) 1/2, proteins that regulate actin polymerization and stability. Dexamethasone treatment of adult hippocampal slices also increased numbers of PSD95+ spines containing pERK1/2, but reduced numbers of pCofilin-immunoreactive spines. Dexamethasone-induced increases in synaptic pERK1/2 were blocked by the GR antagonist RU-486. These results demonstrate that GRs are present in hippocampal spines where they mediate acute glucocorticoid effects on local spine signaling. Through effects on these actin regulatory pathways, GRs are positioned to exert acute effects on synaptic plasticity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / metabolism
  • Actin Depolymerizing Factors / metabolism
  • Actins / metabolism*
  • Animals
  • Dendritic Spines / drug effects
  • Dendritic Spines / enzymology
  • Dendritic Spines / metabolism*
  • Dexamethasone / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fragile X Mental Retardation Protein / metabolism
  • Glucocorticoids / pharmacology
  • Green Fluorescent Proteins / metabolism
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Protein Transport / drug effects
  • Pyramidal Cells / cytology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucocorticoid / metabolism*
  • Receptors, Metabotropic Glutamate / metabolism
  • Signal Transduction* / drug effects
  • Synapses / drug effects
  • Synapses / metabolism
  • Synaptosomes / drug effects
  • Synaptosomes / enzymology
  • p21-Activated Kinases / metabolism


  • Actin Depolymerizing Factors
  • Actins
  • Glucocorticoids
  • Receptors, Glucocorticoid
  • Receptors, Metabotropic Glutamate
  • Fragile X Mental Retardation Protein
  • Green Fluorescent Proteins
  • Dexamethasone
  • p21-Activated Kinases
  • Extracellular Signal-Regulated MAP Kinases