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

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.