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Neuroplasticity pathways and protein-interaction networks are modulated by vortioxetine in rodents

BACKGROUND: The identification of biomarkers that predict susceptibility to major depressive disorder and treatment response to antidepressants is a major challenge. Vortioxetine is a novel multimodal antidepressant that possesses pro-cognitive properties and differentiates from other conventional a...

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Autores principales: Waller, Jessica A., Nygaard, Sara Holm, Li, Yan, du Jardin, Kristian Gaarn, Tamm, Joseph A., Abdourahman, Aicha, Elfving, Betina, Pehrson, Alan L., Sánchez, Connie, Wernersson, Rasmus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543755/
https://www.ncbi.nlm.nih.gov/pubmed/28778148
http://dx.doi.org/10.1186/s12868-017-0376-x
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author Waller, Jessica A.
Nygaard, Sara Holm
Li, Yan
du Jardin, Kristian Gaarn
Tamm, Joseph A.
Abdourahman, Aicha
Elfving, Betina
Pehrson, Alan L.
Sánchez, Connie
Wernersson, Rasmus
author_facet Waller, Jessica A.
Nygaard, Sara Holm
Li, Yan
du Jardin, Kristian Gaarn
Tamm, Joseph A.
Abdourahman, Aicha
Elfving, Betina
Pehrson, Alan L.
Sánchez, Connie
Wernersson, Rasmus
author_sort Waller, Jessica A.
collection PubMed
description BACKGROUND: The identification of biomarkers that predict susceptibility to major depressive disorder and treatment response to antidepressants is a major challenge. Vortioxetine is a novel multimodal antidepressant that possesses pro-cognitive properties and differentiates from other conventional antidepressants on various cognitive and plasticity measures. The aim of the present study was to identify biological systems rather than single biomarkers that may underlie vortioxetine’s treatment effects. RESULTS: We show that the biological systems regulated by vortioxetine are overlapping between mouse and rat in response to distinct treatment regimens and in different brain regions. Furthermore, analysis of complexes of physically-interacting proteins reveal that biomarkers involved in transcriptional regulation, neurodevelopment, neuroplasticity, and endocytosis are modulated by vortioxetine. A subsequent qPCR study examining the expression of targets in the protein–protein interactome space in response to chronic vortioxetine treatment over a range of doses provides further biological validation that vortioxetine engages neuroplasticity networks. Thus, the same biology is regulated in different species and sexes, different brain regions, and in response to distinct routes of administration and regimens. CONCLUSIONS: A recurring theme, based on the present study as well as previous findings, is that networks related to synaptic plasticity, synaptic transmission, signal transduction, and neurodevelopment are modulated in response to vortioxetine treatment. Regulation of these signaling pathways by vortioxetine may underlie vortioxetine’s cognitive-enhancing properties. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12868-017-0376-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-55437552017-08-07 Neuroplasticity pathways and protein-interaction networks are modulated by vortioxetine in rodents Waller, Jessica A. Nygaard, Sara Holm Li, Yan du Jardin, Kristian Gaarn Tamm, Joseph A. Abdourahman, Aicha Elfving, Betina Pehrson, Alan L. Sánchez, Connie Wernersson, Rasmus BMC Neurosci Research Article BACKGROUND: The identification of biomarkers that predict susceptibility to major depressive disorder and treatment response to antidepressants is a major challenge. Vortioxetine is a novel multimodal antidepressant that possesses pro-cognitive properties and differentiates from other conventional antidepressants on various cognitive and plasticity measures. The aim of the present study was to identify biological systems rather than single biomarkers that may underlie vortioxetine’s treatment effects. RESULTS: We show that the biological systems regulated by vortioxetine are overlapping between mouse and rat in response to distinct treatment regimens and in different brain regions. Furthermore, analysis of complexes of physically-interacting proteins reveal that biomarkers involved in transcriptional regulation, neurodevelopment, neuroplasticity, and endocytosis are modulated by vortioxetine. A subsequent qPCR study examining the expression of targets in the protein–protein interactome space in response to chronic vortioxetine treatment over a range of doses provides further biological validation that vortioxetine engages neuroplasticity networks. Thus, the same biology is regulated in different species and sexes, different brain regions, and in response to distinct routes of administration and regimens. CONCLUSIONS: A recurring theme, based on the present study as well as previous findings, is that networks related to synaptic plasticity, synaptic transmission, signal transduction, and neurodevelopment are modulated in response to vortioxetine treatment. Regulation of these signaling pathways by vortioxetine may underlie vortioxetine’s cognitive-enhancing properties. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12868-017-0376-x) contains supplementary material, which is available to authorized users. BioMed Central 2017-08-04 /pmc/articles/PMC5543755/ /pubmed/28778148 http://dx.doi.org/10.1186/s12868-017-0376-x Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Waller, Jessica A.
Nygaard, Sara Holm
Li, Yan
du Jardin, Kristian Gaarn
Tamm, Joseph A.
Abdourahman, Aicha
Elfving, Betina
Pehrson, Alan L.
Sánchez, Connie
Wernersson, Rasmus
Neuroplasticity pathways and protein-interaction networks are modulated by vortioxetine in rodents
title Neuroplasticity pathways and protein-interaction networks are modulated by vortioxetine in rodents
title_full Neuroplasticity pathways and protein-interaction networks are modulated by vortioxetine in rodents
title_fullStr Neuroplasticity pathways and protein-interaction networks are modulated by vortioxetine in rodents
title_full_unstemmed Neuroplasticity pathways and protein-interaction networks are modulated by vortioxetine in rodents
title_short Neuroplasticity pathways and protein-interaction networks are modulated by vortioxetine in rodents
title_sort neuroplasticity pathways and protein-interaction networks are modulated by vortioxetine in rodents
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543755/
https://www.ncbi.nlm.nih.gov/pubmed/28778148
http://dx.doi.org/10.1186/s12868-017-0376-x
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