| First Author | Sarrazin N | Year | 2009 |
| Journal | PLoS One | Volume | 4 |
| Issue | 11 | Pages | e7704 |
| PubMed ID | 19888328 | Mgi Jnum | J:155429 |
| Mgi Id | MGI:4413645 | Doi | 10.1371/journal.pone.0007704 |
| Citation | Sarrazin N, et al. (2009) Transcriptional effects of glucocorticoid receptors in the dentate gyrus increase anxiety-related behaviors. PLoS One 4(11):e7704 |
| abstractText | 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. |
