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Inhibition of NFkB DNA binding activity by glucocorticoids in rat brain

T Unlap1, R S Jope

  • 1Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham 35294, USA.

Neuroscience Letters
|September 22, 1995
PubMed

Insights

Glucocorticoids inhibit the activity of the transcription factor NFkB (nuclear factor kappa B) in the rat brain. This finding suggests a mechanism for how prolonged high glucocorticoid levels may harm neuronal function.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Endocrinology

Background:

  • Glucocorticoids are stress hormones known to affect brain function.
  • Transcription factors regulate gene expression and are crucial for neuronal activity.
  • Previous research indicated glucocorticoids inhibit the transcription factor AP-1.

Purpose of the Study:

  • To investigate the influence of glucocorticoids on the transcription factor NFkB in the rat brain.
  • To determine if glucocorticoids inhibit NFkB DNA binding activity in vivo.

Main Methods:

  • Utilized the gel mobility shift assay.
  • Prepared nuclear extracts from rat cerebral cortex and hippocampus.
  • Administered in vivo treatments including kainate, pilocarpine, and lithium plus pilocarpine-induced seizures.

Main Results:

  • NFkB DNA binding activity was significantly higher in adrenalectomized rats compared to adrenal-intact rats across all tested treatments.
  • This indicates that endogenous glucocorticoids normally inhibit NFkB activity in the rat brain.
  • Demonstrated that glucocorticoids inhibit NFkB, similar to their previously shown inhibition of AP-1.

Conclusions:

  • Glucocorticoids inhibit NFkB activity in the rat brain.
  • This inhibition occurs in both the cortex and hippocampus.
  • Impaired stimulus-induced transcription factor activity due to elevated glucocorticoids may contribute to neuronal dysfunction.

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