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

Jessica A. Waller, Sara Holm Nygaard, Yan Li, Kristian Gaarn Jardin, Joseph A. Tamm, Aicha Abdourahman, Betina Elfving, Alan L. Pehrson, Connie Sanchez, Rasmus Wernersson

    Research output: Contribution to journalJournal articleResearchpeer-review

    334 Downloads (Pure)

    Abstract

    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.

    Original languageEnglish
    Article number56
    JournalBMC Neuroscience
    Volume18
    Issue number1
    Number of pages15
    ISSN0270-6474
    DOIs
    Publication statusPublished - 2017

    Bibliographical note

    © The Author(s) 2017. This 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.

    Keywords

    • Antidepressant
    • Multimodal
    • Network biology
    • Synaptic plasticity
    • Vortioxetine

    Cite this

    Waller, J. A., Nygaard, S. H., Li, Y., Jardin, K. G., Tamm, J. A., Abdourahman, A., Elfving, B., Pehrson, A. L., Sanchez, C., & Wernersson, R. (2017). Neuroplasticity pathways and protein-interaction networks are modulated by vortioxetine in rodents. BMC Neuroscience, 18(1), [56]. https://doi.org/10.1186/s12868-017-0376-x