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

Tino Unlap, Richard S. Jope

Research output: Contribution to journalArticle

43 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)275-282
Number of pages8
JournalMolecular Brain Research
Volume24
Issue number1-4
DOIs
StatePublished - Jul 1994
Externally publishedYes

Keywords

  • AP-1
  • Dexamethasone
  • Fos
  • Glucocorticoid
  • Immediate early gene
  • Jun

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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