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Authors: Herzog, David P.
Pascual Cuadrado, Diego
Treccani, Giulia
Jene, Tanja
Opitz, Verena
Hasch, Annika
Lutz, Beat
Lieb, Klaus
Sillaber, Inge
van der Kooij, Michael A.
Tiwari, Vijay K.
Müller, Marianne B.
Title: A distinct transcriptional signature of antidepressant response in hippocampal dentate gyrus granule cells
Online publication date: 8-Sep-2021
Year of first publication: 2021
Language: english
Abstract: Major depressive disorder is the most prevalent mental illness worldwide, still its pharmacological treatment is limited by various challenges, such as the large heterogeneity in treatment response and the lack of insight into the neurobiological pathways underlying this phenomenon. To decode the molecular mechanisms shaping antidepressant response and to distinguish those from general paroxetine effects, we used a previously established approach targeting extremes (i.e., good vs poor responder mice). We focused on the dentate gyrus (DG), a subregion of major interest in the context of antidepressant mechanisms. Transcriptome profiling on micro-dissected DG granule cells was performed to (i) reveal cell-type-specific changes in paroxetine-induced gene expression (paroxetine vs vehicle) and (ii) to identify molecular signatures of treatment response within a cohort of paroxetine-treated animals. We identified 112 differentially expressed genes associated with paroxetine treatment. The extreme group comparison (good vs poor responder) yielded 211 differentially expressed genes. General paroxetine effects could be distinguished from treatment response-associated molecular signatures, with a differential gene expression overlap of only 4.6% (15 genes). Biological pathway enrichment and cluster analyses identified candidate mechanisms associated with good treatment response, e.g., neuropeptide signaling, synaptic transmission, calcium signaling, and regulation of glucocorticoid secretion. Finally, we examined glucocorticoid receptor (GR)-dependent regulation of selected response-associated genes to analyze a hypothesized interplay between GR signaling and good antidepressant treatment response. Among the most promising candidates, we suggest potential targets such as the developmental gene Otx2 or Htr2c for further investigations into antidepressant treatment response in the future.
DDC: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
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Journal: Translational Psychiatry
Pages or article number: 4
Publisher: Nature Publishing Group
Publisher place: London
Issue date: 2021
ISSN: 2158-3188
Publisher URL:
Publisher DOI: 10.1038/s41398-020-01136-2
Appears in collections:JGU-Publikationen

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