A 24 h corticosterone exposure exacerbates excitotoxic insult in rat hippocampal slice cultures independently of glucocorticoid receptor activation or protein synthesis

Patrick J. Mulholland, Rachel L. Self, Allison K. Hensley, Hilary J. Little, John M. Littleton, Mark A. Prendergast

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Elevations in circulating concentrations of glucocorticoids (GC) may increase the expression and/or sensitivity of ionotropic transmitter receptors in brain. For example, recent evidence suggests that acute and chronic GC exposure may alter the number and/or function of N-methyl-d-aspartate (NMDA)-type glutamate receptors, effects that may sensitize the brain to excitotoxic insults. The present studies examined the ability of short-term (24 h) corticosterone (CORT) exposure to potentiate NMDA-induced cytotoxicity in rat hippocampal slice cultures. Additional studies evaluated the role of mineralocorticoid (MR) and glucocorticoid receptor (GR) function, as well as de novo protein synthesis, in potentiation of toxicity by corticosterone exposure. Hippocampal slice cultures were exposed to NMDA (20 μM) for 24 h with cytotoxicity assessed by fluorescent detection of propidium iodide uptake. Exposure to NMDA caused significant propidium iodide uptake in each hippocampal region, while 24 h CORT (0.001-1 μM) exposure alone did not significantly increase propidium iodide uptake. Co-exposure of cultures to CORT and NMDA synergistically increased propidium iodide uptake in each hippocampal region, effects that were prevented by co-exposure to a non-toxic concentration of MK-801 (20 μM). In contrast, 24 h exposure with the MR antagonist spironolactone (1-10 μM), the GR antagonist RU-486 (1-10 μM), or the protein synthesis inhibitor cycloheximide (1 μM) failed to reduce the significant increase in propidium iodide uptake. These data suggest that relatively brief elevations in CORT levels may sensitize the hippocampus to injury independently of GC receptor activity and protein synthesis.

Original languageEnglish
Pages (from-to)165-172
Number of pages8
JournalBrain Research
Volume1082
Issue number1
DOIs
StatePublished - Apr 12 2006

Keywords

  • Excitotoxicity
  • Glucocorticoid
  • Hippocampus
  • Propidium iodide
  • Protein synthesis

ASJC Scopus subject areas

  • Neuroscience (all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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