Transcriptional effects of glucocorticoid receptors in the dentate gyrus increase anxiety-related behaviors.
The Glucocorticoid Receptor (GR) is a transcription factor ubiquitously expressed in the brain. Activation of brain GRs by high levels of glucocorticoid (GC) hormones modifies a large variety of physiological and pathological-related behaviors. Unfortunately the specific cellular targets of GR-media...
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2009-11-01
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doaj-1b94afc6f7c84b46a5b1220ffdfc1a3a2020-11-24T21:54:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-11-01411e770410.1371/journal.pone.0007704Transcriptional effects of glucocorticoid receptors in the dentate gyrus increase anxiety-related behaviors.Nadège SarrazinFrancesco Di BlasiValérie Roullot-LacarrièreFrançoise Rougé-PontAnne Le RouxPierre CostetJean-Michel RevestPier Vincenzo PiazzaThe Glucocorticoid Receptor (GR) is a transcription factor ubiquitously expressed in the brain. Activation of brain GRs by high levels of glucocorticoid (GC) hormones modifies a large variety of physiological and pathological-related behaviors. Unfortunately the specific cellular targets of GR-mediated behavioral effects of GC are still largely unknown. To address this issue, we generated a mutated form of the GR called DeltaGR. DeltaGR is a constitutively transcriptionally active form of the GR that is localized in the nuclei and activates transcription without binding to glucocorticoids. Using the tetracycline-regulated system (Tet-OFF), we developed an inducible transgenic approach that allows the expression of the DeltaGR in specific brain areas. We focused our study on a mouse line that expressed DeltaGR almost selectively in the glutamatergic neurons of the dentate gyrus (DG) of the hippocampus. This restricted expression of the DeltaGR increased anxiety-related behaviors without affecting other behaviors that could indirectly influence performance in anxiety-related tests. This behavioral phenotype was also associated with an up-regulation of the MAPK signaling pathway and Egr-1 protein in the DG. These findings identify glutamatergic neurons in the DG as one of the cellular substrate of stress-related pathologies.http://europepmc.org/articles/PMC2765620?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nadège Sarrazin Francesco Di Blasi Valérie Roullot-Lacarrière Françoise Rougé-Pont Anne Le Roux Pierre Costet Jean-Michel Revest Pier Vincenzo Piazza |
spellingShingle |
Nadège Sarrazin Francesco Di Blasi Valérie Roullot-Lacarrière Françoise Rougé-Pont Anne Le Roux Pierre Costet Jean-Michel Revest Pier Vincenzo Piazza Transcriptional effects of glucocorticoid receptors in the dentate gyrus increase anxiety-related behaviors. PLoS ONE |
author_facet |
Nadège Sarrazin Francesco Di Blasi Valérie Roullot-Lacarrière Françoise Rougé-Pont Anne Le Roux Pierre Costet Jean-Michel Revest Pier Vincenzo Piazza |
author_sort |
Nadège Sarrazin |
title |
Transcriptional effects of glucocorticoid receptors in the dentate gyrus increase anxiety-related behaviors. |
title_short |
Transcriptional effects of glucocorticoid receptors in the dentate gyrus increase anxiety-related behaviors. |
title_full |
Transcriptional effects of glucocorticoid receptors in the dentate gyrus increase anxiety-related behaviors. |
title_fullStr |
Transcriptional effects of glucocorticoid receptors in the dentate gyrus increase anxiety-related behaviors. |
title_full_unstemmed |
Transcriptional effects of glucocorticoid receptors in the dentate gyrus increase anxiety-related behaviors. |
title_sort |
transcriptional effects of glucocorticoid receptors in the dentate gyrus increase anxiety-related behaviors. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2009-11-01 |
description |
The Glucocorticoid Receptor (GR) is a transcription factor ubiquitously expressed in the brain. Activation of brain GRs by high levels of glucocorticoid (GC) hormones modifies a large variety of physiological and pathological-related behaviors. Unfortunately the specific cellular targets of GR-mediated behavioral effects of GC are still largely unknown. To address this issue, we generated a mutated form of the GR called DeltaGR. DeltaGR is a constitutively transcriptionally active form of the GR that is localized in the nuclei and activates transcription without binding to glucocorticoids. Using the tetracycline-regulated system (Tet-OFF), we developed an inducible transgenic approach that allows the expression of the DeltaGR in specific brain areas. We focused our study on a mouse line that expressed DeltaGR almost selectively in the glutamatergic neurons of the dentate gyrus (DG) of the hippocampus. This restricted expression of the DeltaGR increased anxiety-related behaviors without affecting other behaviors that could indirectly influence performance in anxiety-related tests. This behavioral phenotype was also associated with an up-regulation of the MAPK signaling pathway and Egr-1 protein in the DG. These findings identify glutamatergic neurons in the DG as one of the cellular substrate of stress-related pathologies. |
url |
http://europepmc.org/articles/PMC2765620?pdf=render |
work_keys_str_mv |
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