Dexamethasone induces cell death which may be blocked by NMDA receptor antagonists but is insensitive to Mg2+ in cerebellar granule neurons

Brain Res. 2006 Jan 27;1070(1):116-23. doi: 10.1016/j.brainres.2005.10.093. Epub 2006 Jan 3.


Since dexamethasone may elevate the Ca2+ influx through NMDA receptors, we have investigated mechanisms of dexamethasone toxicity in rat cerebellar granule neurons. Dexamethasone concentrations over 0.1 microM induced cell death that reached about 20% of the death induced by glutamate. Dexamethasone-induced cell death was reduced by more than 80% by the mineralocorticoid antagonist RU 28318 or the NMDA receptor antagonists MK 801 and CGP 39551, whereas RU 28318 rescued only approximately 30% of cells treated with glutamate, indicating that dexamethasone requires NMDA receptors to induce acute neuronal toxicity and that a fraction of the neurons showed this toxicity. Mg2+ reduced the cell death induced by glutamate at potassium concentrations of 1 mM and 5 mM, but not at 25 mM. In contrast, cell death induced by dexamethasone was not significantly reduced by Mg2+ in any of the potassium concentrations. Both glutamate and dexamethasone induced toxicity with translocation of the apoptosis inducer NGFI-B to the mitochondria seen after 30 min-2 h concomitant with activation of apoptosis inducing factor (AIF) and caspase-3. In conclusion, dexamethasone induces a rapid toxicity which is blocked by NMDA receptor antagonists other than Mg2+, and involves mitochondrial apoptosis inducer NGFI-B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Cell Death / drug effects
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / drug effects*
  • Cerebellum / metabolism
  • Dexamethasone / pharmacology*
  • Excitatory Amino Acid Agonists / pharmacology*
  • Magnesium / pharmacology*
  • Mineralocorticoid Receptor Antagonists / pharmacology
  • Mitochondria / metabolism
  • Mitochondria / physiology
  • Nerve Growth Factor / metabolism
  • Nerve Growth Factor / physiology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Rats
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Spironolactone / analogs & derivatives
  • Spironolactone / pharmacology


  • Excitatory Amino Acid Agonists
  • Mineralocorticoid Receptor Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Spironolactone
  • RU 28318
  • Dexamethasone
  • Nerve Growth Factor
  • Magnesium