Downregulation of the CCAAT-enhancer binding protein beta in deltaFosB transgenic mice and by electroconvulsive seizures.
Previous studies demonstrate that chronic, but not acute electroconvulsive seizures (ECS), increases levels of deltaFosB, 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 deltaFosB mediates long-term plasticity in the hippocampus, we analyzed the gene expression profile of inducible transgenic mice expressing deltaFosB with a highly sensitive microarray assay and a customized computer analysis program. The CCAAT-enhancing binding protein-beta (C/EBPbeta) was identified as one of the genes downregulated by deltaFosB in the hippocampus. The downregulation of C/EBPbeta in the inducible deltaFosB transgenic mice was confirmed by other quantitative assays including real-time RT-PCR and low density dot blotting. Analysis of the C/EBPbeta expression in the hippocampus of rats treated with ECS revealed that the C/EBPbeta mRNA was also downregulated by chronic, but not acute ECS administration, the most effective treatment for depression. Given the reported role of C/EBPbeta in behavioral conditioning models, it is possible that the deltaFosB-mediated downregulation of C/EBPbeta in the hippocampus may be a molecular mechanism by which antidepressants alleviate some of the symptoms of depressed patients.
Chen
Jingshan
J
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508, USA.
Newton
Samuel S
SS
Zeng
Ling
L
Adams
David H
DH
Dow
Anthoni L
AL
Madsen
Torsten M
TM
Nestler
Eric J
EJ
Duman
Ronald S
RS
D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004597:Electroshock; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D022782:CCAAT-Enhancer-Binding Protein-beta; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger