Dexamethasone attenuates kainate-induced AP-1 activation in rat brain.

Academic Article

Abstract

  • The goal of this investigation was to determine if administration of the synthetic glucocorticoid dexamethasone modulates rat brain AP-1 DNA binding activity. Treatment with the selective excitatory amino acid agonist kainate was used to activate AP-1 formation. Kainate (12 mg/kg) administration induced a biphasic activation of AP-1 in rat cerebral cortex and hippocampus with maximal levels observed at 1.5 h and 4.5 h and lower levels at 3 h and 6 h. Kainate also induced biphasic increases in the concentrations of some of the AP-1 constituent proteins (immediate early gene protein products), with initial increases of c-Jun, Fos, and Jun B occurring at 1.5 h and secondary larger increases at 4.5 h, but the level of Jun D was not altered by kainate treatment. Pretreatment with dexamethasone (1 mg/kg) reduced AP-1 activity at both 1.5 h and 4.5 h after kainate administration in both brain regions. Dexamethasone pretreatment did not modify the concentrations of the AP-1 constituent proteins obtained after kainate administration except for a reduction of Jun B levels 1.5 h after kainate. These results demonstrate that elevated glucocorticoid levels reduce the stimulation by kainate of AP-1 activity in rat cortex and hippocampus without causing corresponding decreases in the levels of immediate early gene proteins. Binding of the activated glucocorticoid receptor to c-Jun or Fos is likely to contribute to the decreased AP-1 DNA binding activity following dexamethasone treatment.
  • Authors

    Published In

  • Brain Research  Journal
  • Keywords

  • Animals, Base Sequence, Blotting, Western, Brain, Cerebral Cortex, Dexamethasone, Gene Expression, Genes, Immediate-Early, Hippocampus, Kainic Acid, Kinetics, Male, Molecular Sequence Data, Oligodeoxyribonucleotides, Proto-Oncogene Proteins c-fos, Proto-Oncogene Proteins c-jun, Rats, Rats, Sprague-Dawley, Time Factors, Transcription Factor AP-1
  • Author List

  • Unlap T; Jope RS
  • Start Page

  • 275
  • End Page

  • 282
  • Volume

  • 24
  • Issue

  • 1-4