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

BMC Neuroscience

Research Article

Alan L. Pehrson¹  Jessica A. Waller¹  Connie Sánchez¹  Yan Li¹  Joseph A. Tamm²  Aicha Abdourahman²  Sara Holm Nygaard³  Rasmus Wernersson⁴  Betina Elfving⁵  Kristian Gaarn du Jardin⁵ 

[1] External Sourcing and Scientific Excellence, Lundbeck Research U.S.A., 07652, Paramus, NJ, USA;In Vitro Biology, Lundbeck Research U.S.A., 07652, Paramus, NJ, USA;Intomics A/S, Diplomvej 377, 2800, Lyngby, Denmark;Intomics A/S, Diplomvej 377, 2800, Lyngby, Denmark;Center for Biological Sequence Analysis, Technical University of Denmark, 2800, Lyngby, Denmark;Translational Neuropsychiatry Unit, Aarhus University, 8240, Risskov, Denmark;

关键词: Antidepressant;    Multimodal;    Synaptic plasticity;    Network biology;    Vortioxetine;   

DOI  :  10.1186/s12868-017-0376-x

 received in 2017-04-01, accepted in 2017-07-21,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsWe 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.ConclusionsA 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.

【 授权许可】

CC BY   
© The Author(s) 2017