The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNS

J Neurochem. 1999 Feb;72(2):879-82. doi: 10.1046/j.1471-4159.1999.720879.x.


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) 2beta in frontal cortex (FCx). Both treatments also increased the DNA binding activity of PEBP2 alphabeta 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Affect / drug effects
  • Animals
  • Antimanic Agents / pharmacology*
  • Brain Chemistry / drug effects*
  • Frontal Lobe / chemistry
  • Gene Expression / physiology
  • Lithium / pharmacology*
  • Male
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Inbred WKY
  • Transcription Factors / physiology
  • Valproic Acid / pharmacology*


  • Antimanic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Transcription Factors
  • Valproic Acid
  • Lithium