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| Status |
Public on Jul 02, 2015 |
| Title |
Molecular regulation in the hippocampal dentate gyrus in the onset and treatment of depression |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
Major depression is a multidimensional disorder highly prevalent in modern society. Although several classes of antidepressants (ADs) are currently available to treat depression, the effectiveness of treatment is still limited, as many patients do not show full remission; thus, there is a need to find better patients’ directed therapeutic strategies. Neuroplastic changes in several brain regions, namely in the hippocampal dentate gyrus (DG), are amongst the best correlates of depression and of ADs actions. In this study the targets and molecular mediators of chronic stress and of four ADs from different pharmacological classes (fluoxetine, imipramine, tianeptine and agomelatine) were investigated in the DG.
Using the unpredictable chronic mild stress (uCMS) animal model of depression, the molecular commonalities and specificities of the ADs were determined. All ADs, except agomelatine, could reverse the behavioral deficits produced by uCMS, and the neuroplastic changes in the DG; agomelatine reversed only the anhedonic profile in the sucrose consumption test. Chronic stress induced mild but relevant molecular changes that were mostly reversed by fluoxetine, imipramine and tianeptine. Fluoxetine reduced pro-inflammatory response and increased cell metabolism pathways. Its actions were mostly dependent on molecular changes occurring in neurons. Similarities were found between imipramine and tianeptine molecular actions and targets, as both activated pathways related to cellular protection. Moreover, no particular neural cell type enrichment was found with both treatments. Agomelatine presented a very dissimilar molecular pattern impacting greatly on Rho-GTPases-related pathways in oligodendrocytes and neurons. The recognition of these molecular alterations contributes to the understanding of the processes implicated in the onset and treatment of depression and may pave the way for more effective therapeutic interventions.
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| Overall design |
We compared gene expresssion in the dentate gyros of rats which were either untreated, exposed to unpredictable chronic mild stress, or exposed to the same stress and treated with either fluoxetine, imipramine, tianeptine, or agomelatine
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| Contributor(s) |
Patrício P, Mateus-Pinheiro A, Irmler M, Alves ND, Machado-Santos AR, Morais M, Correia JS, Korostynski M, Piechota M, Beckers J, Bessa JM, Almeida OF, Sousa N, Pinto L |
| Citation(s) |
25035085, 32848656 |
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| Submission date |
Mar 19, 2014 |
| Last update date |
Aug 31, 2020 |
| Contact name |
Johannes Beckers |
| E-mail(s) |
johannes.beckers@helmholtz-munich.de
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| Organization name |
Helmholtz Zentrum Muenchen
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| Department |
Institute of Experimental Genetics
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| Street address |
Ingolstaedter Landstr. 1
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| City |
Neuherberg |
| ZIP/Postal code |
85764 |
| Country |
Germany |
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| Platforms (1) |
| GPL6247 |
[RaGene-1_0-st] Affymetrix Rat Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (21)
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| GSM1350791 |
Unpredictable chronic mild stress, biological replicate 1 |
| GSM1350792 |
Unpredictable chronic mild stress, biological replicate 2 |
| GSM1350793 |
Unpredictable chronic mild stress, biological replicate 3 |
| GSM1350794 |
Unpredictable chronic mild stress, agomelatine treatment, biological replicate 1 |
| GSM1350795 |
Unpredictable chronic mild stress, agomelatine treatment, biological replicate 2 |
| GSM1350796 |
Unpredictable chronic mild stress, agomelatine treatment, biological replicate 3 |
| GSM1350797 |
Unpredictable chronic mild stress, fluoxetine treatment, biological replicate 1 |
| GSM1350798 |
Unpredictable chronic mild stress, fluoxetine treatment, biological replicate 2 |
| GSM1350799 |
Unpredictable chronic mild stress, fluoxetine treatment, biological replicate 3 |
| GSM1350800 |
Unpredictable chronic mild stress, imipramine treatment, biological replicate 1 |
| GSM1350801 |
Unpredictable chronic mild stress, imipramine treatment, biological replicate 2 |
| GSM1350802 |
Unpredictable chronic mild stress, imipramine treatment, biological replicate 3 |
| GSM1350803 |
Unpredictable chronic mild stress, tianeptine treatment, biological replicate 1 |
| GSM1350804 |
Unpredictable chronic mild stress, tianeptine treatment, biological replicate 2 |
| GSM1350805 |
Unpredictable chronic mild stress, tianeptine treatment, biological replicate 3 |
| GSM1350806 |
Untreated control, biological replicate 1 |
| GSM1350807 |
Untreated control, biological replicate 2 |
| GSM1350808 |
Untreated control, biological replicate 3 |
| GSM1350809 |
Untreated control, technical replicate of CTRL_1 |
| GSM1350810 |
Untreated control, technical replicate of CTRL_2 |
| GSM1350811 |
Untreated control, technical replicate of CTRL_3 |
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| Relations |
| BioProject |
PRJNA242258 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE56028_RAW.tar |
93.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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