Corticosterone acutely prolonged N-methyl-d-aspartate receptor-mediated Ca2+ elevation in cultured rat hippocampal neurons

J Neurochem. 2002 Dec;83(6):1441-51. doi: 10.1046/j.1471-4159.2002.01251.x.


This work reports the first demonstration that corticosterone (CORT) has a rapid and transient effect on NMDA receptor-mediated Ca2+ signaling in cultured rat hippocampal neurons. Using single cell Ca2+ imaging, CORT and agonists of glucocorticoid receptors were observed to modulate the NMDA receptor-mediated Ca2+ signals in a completely different fashion from pregnenolone sulfate. In the absence of steroids, 100 micro m NMDA induced a transient Ca2+ signal that lasted for 30-70 s in 86.1% of the neurons prepared from postnatal rats (3-5 days old). After pre-treatment with 0.1-100 micro m CORT for 10-20 min, NMDA induced extremely prolonged Ca2+ elevation. This prolonged Ca2+ elevation was terminated by the application of MK-801 and followed by washing out of CORT. The proportion of CORT-modulated neurons within the NMDA-responsive cells increased from 25.1 to 95.5% when the concentration of CORT was raised from 0.1 to 50 micro m. Substitution of BSA-conjugated CORT produced essentially the same results. When hippocampal neurons were preincubated with 10 micro m cortisol and 1 micro m dexamethasone for 20 min, a very prolonged Ca2+ elevation was also observed upon NMDA stimulation. The CORT-prolonged Ca2+ elevation caused a long-lasting depolarization of the mitochondrial membrane, as observed with rhodamine 123. In contrast, incubation with 100 micro m pregnenolone sulfate did not considerably alter the time duration of NMDA-induced transient Ca2+ elevation, but caused a significant increase in the peak amplitude of Ca2+ elevation in hippocampal neurons. These results imply that high levels of CORT induce a rapid and non-genomic prolongation of NMDA receptor-mediated Ca2+ elevation, probably via putative membrane surface receptors for CORT in the hippocampal neurons.

MeSH terms

  • Androstanols / pharmacology
  • Animals
  • Calcium / metabolism*
  • Calcium Signaling / drug effects
  • Cells, Cultured
  • Corticosterone / pharmacology*
  • Dizocilpine Maleate / pharmacology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Fluorescent Dyes
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hormone Antagonists / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mifepristone / pharmacology
  • Mitochondria / drug effects
  • Mitochondria / physiology
  • N-Methylaspartate / pharmacology
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Pregnenolone / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Glucocorticoid / agonists
  • Receptors, Glucocorticoid / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / agonists
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism*


  • Androstanols
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Fluorescent Dyes
  • Hormone Antagonists
  • Receptors, Glucocorticoid
  • Receptors, N-Methyl-D-Aspartate
  • pregnenolone sulfate
  • Mifepristone
  • N-Methylaspartate
  • Dizocilpine Maleate
  • Pregnenolone
  • 11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one
  • Calcium
  • Corticosterone