{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T07:03:39Z","timestamp":1792479819379,"version":"4.5.0"},"reference-count":67,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["MH133268"],"award-info":[{"award-number":["MH133268"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000874","name":"Brain and Behavior Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000874","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006694","name":"McLean Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006694","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Post\u2010traumatic stress disorder (PTSD) and major depressive disorder (MDD) are debilitating stress\u2010related psychiatric disorders that can develop following exposure to traumatic events or chronic stress in some individuals. The neurobiological processes leading to disease remain largely unknown. Among others, these disorders are characterized by a dysregulated hypothalamic\u2013pituitary\u2013adrenal axis, which is regulated by the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). This leads to altered downstream corticosteroid\u2010induced gene expression. In vitro models are promising tools to investigate specific neurobiological underpinnings of the stress response in the brain. Here, we investigated the suitability of SH\u2010SY5Y\u2010derived neurons as a cost\u2010efficient system to study the role of GR and MR in the neuronal stress response. SH\u2010SY5Y\u2010derived neurons were characterized, exposed to corticosteroids, and analyzed on transcriptomic and proteomic levels. We show that (i) these neurons express sufficient and seemingly functional GR and MR to allow the study of corticosteroid\u2010induced transcription, (ii) three corticosteroids cortisol, dexamethasone, and aldosterone, induced similar transcriptomic effects, (iii) the antagonist spironolactone mildly attenuated the effects of dexamethasone in\n                    <jats:italic>FKBP5<\/jats:italic>\n                    ,\n                    <jats:italic>DUSP1<\/jats:italic>\n                    , and\n                    <jats:italic>SUPV3L1<\/jats:italic>\n                    . Mifepristone did not significantly alter the effect of aldosterone. (iv) Integrating transcriptomic alterations of these corticosteroid\u2010exposed neurons with those of iPSC\u2010derived neurons exposed to dexamethasone showed concordant corticosteroid\u2010induced effects in the two in vitro systems. To determine translational validity, we compared the gene expression in these neurons with the transcriptome of postmortem brain samples from individuals with PTSD and MDD, yielding stronger negative correlations of corticosteroid effects in SH\u2010SY5Y\u2010derived neurons with PTSD signatures than with MDD signatures. Upon further refinement and validation, SH\u2010SY5Y\u2010derived neurons may serve as a simplistic tool to study neuronal corticosteroid\u2010induced gene expression and the implicated molecular networks around GR and MR. Strengthening our insight into these receptors' functions improves our understanding of the hypothalamic\u2013pituitary\u2013adrenal axis, which is commonly altered in stress\u2010related psychiatric disorders such as PTSD and MDD.\n                  <\/jats:p>","DOI":"10.1111\/jne.70021","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T02:32:29Z","timestamp":1742437949000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Corticosteroid\u2010regulated gene transcription in\n                    <scp>SH<\/scp>\n                    \u2010\n                    <scp>SY5Y<\/scp>\n                    \u2010derived neurons: Insights into the mineralocorticoid and glucocorticoid receptor\u2010mediated response"],"prefix":"10.1111","volume":"37","author":[{"given":"Justina F.","family":"Lugenb\u00fchl","sequence":"first","affiliation":[{"name":"Department of Psychiatry McLean Hospital, Harvard Medical School  Belmont Massachusetts USA"},{"name":"Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"},{"name":"Department of Psychiatry and Neuropsychology School for Mental Health and Neuroscience (MHeNs) and European Graduate School of Neuroscience (EURON), Faculty of Health, Medicine and Life Sciences (FHML) Maastricht University  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Snijders","sequence":"additional","affiliation":[{"name":"Department of Psychiatry McLean Hospital, Harvard Medical School  Belmont Massachusetts USA"},{"name":"Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron D.","family":"Pernia","sequence":"additional","affiliation":[{"name":"Department of Psychiatry McLean Hospital, Harvard Medical School  Belmont Massachusetts USA"},{"name":"Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina Soliva","family":"Estruch","sequence":"additional","affiliation":[{"name":"Department of Psychiatry McLean Hospital, Harvard Medical School  Belmont Massachusetts USA"},{"name":"Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"},{"name":"Department of Psychiatry and Neuropsychology School for Mental Health and Neuroscience (MHeNs) and European Graduate School of Neuroscience (EURON), Faculty of Health, Medicine and Life Sciences (FHML) Maastricht University  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunter","family":"Kenis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuropsychology School for Mental Health and Neuroscience (MHeNs) and European Graduate School of Neuroscience (EURON), Faculty of Health, Medicine and Life Sciences (FHML) Maastricht University  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1660-9112","authenticated-orcid":false,"given":"Nikolaos P.","family":"Daskalakis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry McLean Hospital, Harvard Medical School  Belmont Massachusetts USA"},{"name":"Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"},{"name":"Department of Psychiatry and Neuropsychology School for Mental Health and Neuroscience (MHeNs) and European Graduate School of Neuroscience (EURON), Faculty of Health, Medicine and Life Sciences (FHML) Maastricht University  Maastricht the 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