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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...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1855984/ https://www.ncbi.nlm.nih.gov/pubmed/17487276 http://dx.doi.org/10.1371/journal.pone.0000431 |
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author | Böer, Ulrike Alejel, Tahseen Beimesche, Stephan Cierny, Irmgard Krause, Doris Knepel, Willhart Flügge, Gabriele |
author_facet | Böer, Ulrike Alejel, Tahseen Beimesche, Stephan Cierny, Irmgard Krause, Doris Knepel, Willhart Flügge, Gabriele |
author_sort | Böer, Ulrike |
collection | PubMed |
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 (2×10 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. |
format | Text |
id | pubmed-1855984 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-18559842007-05-09 CRE/CREB-Driven Up-Regulation of Gene Expression by Chronic Social Stress in CRE-Luciferase Transgenic Mice: Reversal by Antidepressant Treatment Böer, Ulrike Alejel, Tahseen Beimesche, Stephan Cierny, Irmgard Krause, Doris Knepel, Willhart Flügge, Gabriele PLoS One Research Article 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 (2×10 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. Public Library of Science 2007-05-09 /pmc/articles/PMC1855984/ /pubmed/17487276 http://dx.doi.org/10.1371/journal.pone.0000431 Text en Boeer et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Böer, Ulrike Alejel, Tahseen Beimesche, Stephan Cierny, Irmgard Krause, Doris Knepel, Willhart Flügge, Gabriele CRE/CREB-Driven Up-Regulation of Gene Expression by Chronic Social Stress in CRE-Luciferase Transgenic Mice: Reversal by Antidepressant Treatment |
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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1855984/ https://www.ncbi.nlm.nih.gov/pubmed/17487276 http://dx.doi.org/10.1371/journal.pone.0000431 |
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