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 Citations (Scopus)

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
StatePublished - Jan 1 2004

Fingerprint

CCAAT-Enhancer-Binding Proteins
Transgenic Mice
Carrier Proteins
Seizures
Down-Regulation
Hippocampus
Antidepressive Agents
Transcriptome
Real-Time Polymerase Chain Reaction
Transcription Factors
Software
Messenger RNA
Therapeutics
Genes

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 journalArticle

Chen, Jingshan ; Newton, Samuel S. ; Zeng, Ling ; Adams, David H. ; Dow, Anthoni L. ; Madsen, Torsten M. ; Nestler, Eric J. ; Duman, Ronald S. / Downregulation of the CCAAT-Enhancer Binding Protein β in ΔFosB Transgenic Mice and by Electroconvulsive Seizures. In: Neuropsychopharmacology. 2004 ; Vol. 29, No. 1. pp. 23-31.
@article{d15071534bdf45459b2501924e28e867,
title = "Downregulation of the CCAAT-Enhancer Binding Protein β in ΔFosB Transgenic Mice and by Electroconvulsive Seizures",
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.",
keywords = "Antidepressant, C/EBPβ, Hippocampus, Memory, Microarray, ΔFosB",
author = "Jingshan Chen and Newton, {Samuel S.} and Ling Zeng and Adams, {David H.} and Dow, {Anthoni L.} and Madsen, {Torsten M.} and Nestler, {Eric J.} and Duman, {Ronald S.}",
year = "2004",
month = "1",
day = "1",
doi = "10.1038/sj.npp.1300289",
language = "English (US)",
volume = "29",
pages = "23--31",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "1",

}

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 -