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Keywords:

  • Lithium;
  • Valproate;
  • Bcl-2;
  • Manic-depressive illness;
  • Transcription factors;
  • Polyomavirus enhancer;
  • binding protein 2;
  • Differential display

Abstract : Differential display of mRNA was used to identify concordant changes in gene expression induced by two mood-stabilizing agents, lithium and valproate (VPA). Both treatments, on chronic administration, increased mRNA levels of the transcription factor polyomavirus enhancer-binding protein (PEBP) 2β in frontal cortex (FCx). Both treatments also increased the DNA binding activity of PEBP2αβ and robustly increased the levels of bcl-2 (known to be transcriptionally regulated by PEBP2) in FCx. Immunohistochemical studies revealed a marked increase in the number of bcl-2-immunoreactive cells in layers 2 and 3 of FCx. These novel findings represent the first report of medication-induced increases in CNS bcl-2 levels and may have implications not only for mood disorders, but also for long-term treatment of various neurodegenerative disorders.