Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-6318
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dc.contributor.authorHerzog, David P.-
dc.contributor.authorPascual Cuadrado, Diego-
dc.contributor.authorTreccani, Giulia-
dc.contributor.authorJene, Tanja-
dc.contributor.authorOpitz, Verena-
dc.contributor.authorHasch, Annika-
dc.contributor.authorLutz, Beat-
dc.contributor.authorLieb, Klaus-
dc.contributor.authorSillaber, Inge-
dc.contributor.authorvan der Kooij, Michael A.-
dc.contributor.authorTiwari, Vijay K.-
dc.contributor.authorMüller, Marianne B.-
dc.date.accessioned2021-09-08T10:45:08Z-
dc.date.available2021-09-08T10:45:08Z-
dc.date.issued2021-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/6328-
dc.description.abstractMajor 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.en_GB
dc.language.isoengde
dc.rightsCC BY*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleA distinct transcriptional signature of antidepressant response in hippocampal dentate gyrus granule cellsen_GB
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-6318-
jgu.type.dinitypearticleen_GB
jgu.type.versionPublished versionde
jgu.type.resourceTextde
jgu.organisation.departmentFB 04 Medizinde
jgu.organisation.number2700-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titleTranslational Psychiatryde
jgu.journal.volume11de
jgu.pages.alternative4de
jgu.publisher.year2021-
jgu.publisher.nameNature Publishing Groupde
jgu.publisher.placeLondonde
jgu.publisher.urihttps://doi.org/10.1038/s41398-020-01136-2de
jgu.publisher.issn2158-3188de
jgu.organisation.placeMainz-
jgu.subject.ddccode610de
jgu.publisher.doi10.1038/s41398-020-01136-2-
jgu.organisation.rorhttps://ror.org/023b0x485-
Appears in collections:JGU-Publikationen

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