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Delineation of molecular pathway activities of the chronic antidepressant treatment response suggests important roles for glutamatergic and ubiquitin–proteasome systems
The aim of this study was to identify molecular pathways related to antidepressant response. We administered paroxetine to the DBA/2J mice for 28 days. Following the treatment, the mice were grouped into responders or non-responders depending on the time they spent immobile in the forced swim test....
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5416684/ https://www.ncbi.nlm.nih.gov/pubmed/28375208 http://dx.doi.org/10.1038/tp.2017.39 |
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author | Park, D I Dournes, C Sillaber, I Ising, M Asara, J M Webhofer, C Filiou, M D Müller, M B Turck, C W |
author_facet | Park, D I Dournes, C Sillaber, I Ising, M Asara, J M Webhofer, C Filiou, M D Müller, M B Turck, C W |
author_sort | Park, D I |
collection | PubMed |
description | The aim of this study was to identify molecular pathways related to antidepressant response. We administered paroxetine to the DBA/2J mice for 28 days. Following the treatment, the mice were grouped into responders or non-responders depending on the time they spent immobile in the forced swim test. Hippocampal metabolomics and proteomics analyses revealed that chronic paroxetine treatment affects glutamate-related metabolite and protein levels differentially in the two groups. We found significant differences in the expression of N-methyl-d-aspartate receptor and neuronal nitric oxide synthase proteins between the two groups, without any significant alterations in the respective transcript levels. In addition, we found that chronic paroxetine treatment altered the levels of proteins associated with the ubiquitin–proteasome system (UPS). The soluble guanylate cyclase-β1, proteasome subunit α type-2 and ubiquitination levels were also affected in peripheral blood mononuclear cells from antidepressant responder and non-responder patients suffering from major depressive disorder. We submit that the glutamatergic system and UPS have a crucial role in the antidepressant treatment response in both mice and humans. |
format | Online Article Text |
id | pubmed-5416684 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-54166842017-05-16 Delineation of molecular pathway activities of the chronic antidepressant treatment response suggests important roles for glutamatergic and ubiquitin–proteasome systems Park, D I Dournes, C Sillaber, I Ising, M Asara, J M Webhofer, C Filiou, M D Müller, M B Turck, C W Transl Psychiatry Original Article The aim of this study was to identify molecular pathways related to antidepressant response. We administered paroxetine to the DBA/2J mice for 28 days. Following the treatment, the mice were grouped into responders or non-responders depending on the time they spent immobile in the forced swim test. Hippocampal metabolomics and proteomics analyses revealed that chronic paroxetine treatment affects glutamate-related metabolite and protein levels differentially in the two groups. We found significant differences in the expression of N-methyl-d-aspartate receptor and neuronal nitric oxide synthase proteins between the two groups, without any significant alterations in the respective transcript levels. In addition, we found that chronic paroxetine treatment altered the levels of proteins associated with the ubiquitin–proteasome system (UPS). The soluble guanylate cyclase-β1, proteasome subunit α type-2 and ubiquitination levels were also affected in peripheral blood mononuclear cells from antidepressant responder and non-responder patients suffering from major depressive disorder. We submit that the glutamatergic system and UPS have a crucial role in the antidepressant treatment response in both mice and humans. Nature Publishing Group 2017-04 2017-04-04 /pmc/articles/PMC5416684/ /pubmed/28375208 http://dx.doi.org/10.1038/tp.2017.39 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Park, D I Dournes, C Sillaber, I Ising, M Asara, J M Webhofer, C Filiou, M D Müller, M B Turck, C W Delineation of molecular pathway activities of the chronic antidepressant treatment response suggests important roles for glutamatergic and ubiquitin–proteasome systems |
title | Delineation of molecular pathway activities of the chronic antidepressant treatment response suggests important roles for glutamatergic and ubiquitin–proteasome systems |
title_full | Delineation of molecular pathway activities of the chronic antidepressant treatment response suggests important roles for glutamatergic and ubiquitin–proteasome systems |
title_fullStr | Delineation of molecular pathway activities of the chronic antidepressant treatment response suggests important roles for glutamatergic and ubiquitin–proteasome systems |
title_full_unstemmed | Delineation of molecular pathway activities of the chronic antidepressant treatment response suggests important roles for glutamatergic and ubiquitin–proteasome systems |
title_short | Delineation of molecular pathway activities of the chronic antidepressant treatment response suggests important roles for glutamatergic and ubiquitin–proteasome systems |
title_sort | delineation of molecular pathway activities of the chronic antidepressant treatment response suggests important roles for glutamatergic and ubiquitin–proteasome systems |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5416684/ https://www.ncbi.nlm.nih.gov/pubmed/28375208 http://dx.doi.org/10.1038/tp.2017.39 |
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