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 language | English (US) |
|---|---|
| Pages (from-to) | 23-31 |
| Number of pages | 9 |
| Journal | Neuropsychopharmacology |
| Volume | 29 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2004 |
Fingerprint
Keywords
- Antidepressant
- C/EBPβ
- Hippocampus
- Memory
- Microarray
- ΔFosB
ASJC Scopus subject areas
- Pharmacology
- Psychiatry and Mental health
Cite this
Downregulation of the CCAAT-Enhancer Binding Protein β in ΔFosB Transgenic Mice and by Electroconvulsive Seizures. / Chen, Jingshan; Newton, Samuel S.; Zeng, Ling; Adams, David H.; Dow, Anthoni L.; Madsen, Torsten M.; Nestler, Eric J.; Duman, Ronald S.
In: Neuropsychopharmacology, Vol. 29, No. 1, 01.01.2004, p. 23-31.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Downregulation of the CCAAT-Enhancer Binding Protein β in ΔFosB Transgenic Mice and by Electroconvulsive Seizures
AU - Chen, Jingshan
AU - Newton, Samuel S.
AU - Zeng, Ling
AU - Adams, David H.
AU - Dow, Anthoni L.
AU - Madsen, Torsten M.
AU - Nestler, Eric J.
AU - Duman, Ronald S.
PY - 2004/1/1
Y1 - 2004/1/1
N2 - 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.
AB - 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.
KW - Antidepressant
KW - C/EBPβ
KW - Hippocampus
KW - Memory
KW - Microarray
KW - ΔFosB
UR - http://www.scopus.com/inward/record.url?scp=0346688567&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0346688567&partnerID=8YFLogxK
U2 - 10.1038/sj.npp.1300289
DO - 10.1038/sj.npp.1300289
M3 - Article
C2 - 14532910
AN - SCOPUS:0346688567
VL - 29
SP - 23
EP - 31
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
IS - 1
ER -