Downregulation of the CCAAT-Enhancer Binding Protein β in ΔFosB Transgenic Mice and by Electroconvulsive Seizures

Jingshan Chen, Samuel S. Newton, Ling Zeng, David H. Adams, Anthoni L. Dow, Torsten M. Madsen, Eric J. Nestler, Ronald S. Duman

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Previous studies demonstrate that chronic, but not acute electroconvulsive seizures (ECS), increases levels of ΔFosB, a long-lasting transcription factor, in the hippocampus, and this effect correlates with the slow onset and long-lasting clinical effects of antidepressant treatment. To understand how ΔFosB mediates long-term plasticity in the hippocampus, we analyzed the gene expression profile of inducible transgenic mice expressing ΔFosB with a highly sensitive microarray assay and a customized computer analysis program. The CCAAT-enhancing binding protein-β (C/EBPβ) was identified as one of the genes downregulated by ΔFosB in the hippocampus. The downregulation of C/EBPβ in the inducible ΔFosB transgenic mice was confirmed by other quantitative assays including real-time RT-PCR and low density dot blotting. Analysis of the C/EBPβ expression in the hippocampus of rats treated with ECS revealed that the C/EBPβ mRNA was also downregulated by chronic, but not acute ECS administration, the most effective treatment for depression. Given the reported role of C/EBPβ in behavioral conditioning models, it is possible that the ΔFosB-mediated downregulation of C/EBPβ in the hippocampus may be a molecular mechanism by which antidepressants alleviate some of the symptoms of depressed patients.

Original languageEnglish (US)
Pages (from-to)23-31
Number of pages9
JournalNeuropsychopharmacology
Volume29
Issue number1
DOIs
Publication statusPublished - Jan 1 2004

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Keywords

  • Antidepressant
  • C/EBPβ
  • Hippocampus
  • Memory
  • Microarray
  • ΔFosB

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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