CRE/CREB-driven up-regulation of gene expression by chronic social stress in CRE-luciferase transgenic mice: reversal by antidepressant treatment.

BACKGROUND: It has been suggested that stress provokes neuropathological changes and may thus contribute to the precipitation of affective disorders such as depression. Likewise, the pharmacological therapy of depression requires chronic treatment and is thought to induce a positive neuronal adaptat...

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Main Authors: Ulrike Böer, Tahseen Alejel, Stephan Beimesche, Irmgard Cierny, Doris Krause, Willhart Knepel, Gabriele Flügge
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2007-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC1855984?pdf=render
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author Ulrike Böer
Tahseen Alejel
Stephan Beimesche
Irmgard Cierny
Doris Krause
Willhart Knepel
Gabriele Flügge
author_facet Ulrike Böer
Tahseen Alejel
Stephan Beimesche
Irmgard Cierny
Doris Krause
Willhart Knepel
Gabriele Flügge
author_sort Ulrike Böer
collection DOAJ
description BACKGROUND: It has been suggested that stress provokes neuropathological changes and may thus contribute to the precipitation of affective disorders such as depression. Likewise, the pharmacological therapy of depression requires chronic treatment and is thought to induce a positive neuronal adaptation, presumably based on changes in gene transcription. The transcription factor cAMP-responsive element binding protein (CREB) and its binding site (CRE) have been suggested to play a major role in both the development of depression and antidepressive therapy. METHODOLOGY/PRINCIPLE FINDINGS: To investigate the impact of stress and antidepressant treatment on CRE/CREB transcriptional activity, we generated a transgenic mouse line in which expression of the luciferase reporter gene is controlled by four copies of CRE. In this transgene, luciferase enzyme activity and protein were detected throughout the brain, e.g., in the hippocampal formation. Chronic social stress significantly increased (by 45 to 120%) CRE/CREB-driven gene expression measured as luciferase activity in several brain regions. This was also reflected by increased CREB-phosphorylation determined by immunoblotting. Treatment of the stressed mice with the antidepressant imipramine normalized luciferase expression to control levels in all brain regions and likewise reduced CREB-phosphorylation. In non-stressed animals, chronic (21 d) but not acute (24 h) treatment with imipramine (2x10 mg/kg/d) reduced luciferase expression in the hippocampus by 40-50%. CONCLUSIONS/SIGNIFICANCE: Our results emphasize a role of CREB in stress-regulated gene expression and support the view that the therapeutic actions of antidepressants are mediated via CRE/CREB-directed transcription.
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spelling doaj.art-b4d03558e7334b3ca6325781d0eec2932022-12-22T01:31:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-01-0125e43110.1371/journal.pone.0000431CRE/CREB-driven up-regulation of gene expression by chronic social stress in CRE-luciferase transgenic mice: reversal by antidepressant treatment.Ulrike BöerTahseen AlejelStephan BeimescheIrmgard CiernyDoris KrauseWillhart KnepelGabriele FlüggeBACKGROUND: It has been suggested that stress provokes neuropathological changes and may thus contribute to the precipitation of affective disorders such as depression. Likewise, the pharmacological therapy of depression requires chronic treatment and is thought to induce a positive neuronal adaptation, presumably based on changes in gene transcription. The transcription factor cAMP-responsive element binding protein (CREB) and its binding site (CRE) have been suggested to play a major role in both the development of depression and antidepressive therapy. METHODOLOGY/PRINCIPLE FINDINGS: To investigate the impact of stress and antidepressant treatment on CRE/CREB transcriptional activity, we generated a transgenic mouse line in which expression of the luciferase reporter gene is controlled by four copies of CRE. In this transgene, luciferase enzyme activity and protein were detected throughout the brain, e.g., in the hippocampal formation. Chronic social stress significantly increased (by 45 to 120%) CRE/CREB-driven gene expression measured as luciferase activity in several brain regions. This was also reflected by increased CREB-phosphorylation determined by immunoblotting. Treatment of the stressed mice with the antidepressant imipramine normalized luciferase expression to control levels in all brain regions and likewise reduced CREB-phosphorylation. In non-stressed animals, chronic (21 d) but not acute (24 h) treatment with imipramine (2x10 mg/kg/d) reduced luciferase expression in the hippocampus by 40-50%. CONCLUSIONS/SIGNIFICANCE: Our results emphasize a role of CREB in stress-regulated gene expression and support the view that the therapeutic actions of antidepressants are mediated via CRE/CREB-directed transcription.http://europepmc.org/articles/PMC1855984?pdf=render
spellingShingle Ulrike Böer
Tahseen Alejel
Stephan Beimesche
Irmgard Cierny
Doris Krause
Willhart Knepel
Gabriele Flügge
CRE/CREB-driven up-regulation of gene expression by chronic social stress in CRE-luciferase transgenic mice: reversal by antidepressant treatment.
PLoS ONE
title CRE/CREB-driven up-regulation of gene expression by chronic social stress in CRE-luciferase transgenic mice: reversal by antidepressant treatment.
title_full CRE/CREB-driven up-regulation of gene expression by chronic social stress in CRE-luciferase transgenic mice: reversal by antidepressant treatment.
title_fullStr CRE/CREB-driven up-regulation of gene expression by chronic social stress in CRE-luciferase transgenic mice: reversal by antidepressant treatment.
title_full_unstemmed CRE/CREB-driven up-regulation of gene expression by chronic social stress in CRE-luciferase transgenic mice: reversal by antidepressant treatment.
title_short CRE/CREB-driven up-regulation of gene expression by chronic social stress in CRE-luciferase transgenic mice: reversal by antidepressant treatment.
title_sort cre creb driven up regulation of gene expression by chronic social stress in cre luciferase transgenic mice reversal by antidepressant treatment
url http://europepmc.org/articles/PMC1855984?pdf=render
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