{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T20:26:15Z","timestamp":1774643175247,"version":"3.50.1"},"reference-count":79,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T00:00:00Z","timestamp":1635552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["IF\/01079\/2014; 2020.02855.CEECIND"],"award-info":[{"award-number":["IF\/01079\/2014; 2020.02855.CEECIND"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nature Research Award for Driving Global Impact - 2019 Brain Sciences","award":["LP"],"award-info":[{"award-number":["LP"]}]},{"name":"FEDER, through the Competitiveness Internationalization Operational Program (POCI)","award":["UIDB\/50026\/2020; UIDP\/50026\/2020; NORTE-01-0145-FEDER-000013; NORTE-01-0145-FEDER-000023"],"award-info":[{"award-number":["UIDB\/50026\/2020; UIDP\/50026\/2020; NORTE-01-0145-FEDER-000013; NORTE-01-0145-FEDER-000023"]}]},{"name":"PPBI - Portuguese Platform of Bioimaging","award":["PPBI-POCI-01-0145-FEDER-022122"],"award-info":[{"award-number":["PPBI-POCI-01-0145-FEDER-022122"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Changes in adult hippocampal cell proliferation and genesis have been largely implicated in depression and antidepressant action, though surprisingly, the underlying cell cycle mechanisms are largely undisclosed. Using both an in vivo unpredictable chronic mild stress (uCMS) rat model of depression and in vitro rat hippocampal-derived neurosphere culture approaches, we aimed to unravel the cell cycle mechanisms regulating hippocampal cell proliferation and genesis in depression and after antidepressant treatment. We show that the hippocampal dentate gyrus (hDG) of uCMS animals have less proliferating cells and a decreased proportion of cells in the G2\/M phase, suggesting a G1 phase arrest; this is accompanied by decreased levels of cyclin D1, E, and A expression. Chronic fluoxetine treatment reversed the G1 phase arrest and promoted an up-regulation of cyclin E. In vitro, dexamethasone (DEX) decreased cell proliferation, whereas the administration of serotonin (5-HT) reversed it. DEX also induced a G1-phase arrest and decreased cyclin D1 and D2 expression levels while increasing p27. Additionally, 5-HT treatment could partly reverse the G1-phase arrest and restored cyclin D1 expression. We suggest that the anti-proliferative actions of chronic stress in the hDG result from a glucocorticoid-mediated G1-phase arrest in the progenitor cells that is partly mediated by decreased cyclin D1 expression which may be overcome by antidepressant treatment.<\/jats:p>","DOI":"10.3390\/ijms222111798","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:21:34Z","timestamp":1635805294000},"page":"11798","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cell Cycle Regulation of Hippocampal Progenitor Cells in Experimental Models of Depression and after Treatment with Fluoxetine"],"prefix":"10.3390","volume":"22","author":[{"given":"Patr\u00edcia","family":"Patr\u00edcio","sequence":"first","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4805-017 Braga\/Guimar\u00e3es, Portugal"},{"name":"B\u2019nML\u2014Behavioral &Molecular Lab, 4715-057 Braga, Portugal"}]},{"given":"Ant\u00f3nio","family":"Mateus-Pinheiro","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4805-017 Braga\/Guimar\u00e3es, Portugal"},{"name":"B\u2019nML\u2014Behavioral &Molecular Lab, 4715-057 Braga, Portugal"}]},{"given":"Ana Rita","family":"Machado-Santos","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4805-017 Braga\/Guimar\u00e3es, Portugal"}]},{"given":"Nuno Dinis","family":"Alves","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4805-017 Braga\/Guimar\u00e3es, Portugal"},{"name":"Department of Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY 10032, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5920-1067","authenticated-orcid":false,"given":"Joana Sofia","family":"Correia","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4805-017 Braga\/Guimar\u00e3es, Portugal"}]},{"given":"M\u00f3nica","family":"Morais","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4805-017 Braga\/Guimar\u00e3es, Portugal"}]},{"given":"Jo\u00e3o Miguel","family":"Bessa","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4805-017 Braga\/Guimar\u00e3es, Portugal"},{"name":"B\u2019nML\u2014Behavioral &Molecular Lab, 4715-057 Braga, Portugal"}]},{"given":"Ana Jo\u00e3o","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4805-017 Braga\/Guimar\u00e3es, Portugal"}]},{"given":"Nuno","family":"Sousa","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4805-017 Braga\/Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7724-0446","authenticated-orcid":false,"given":"Lu\u00edsa","family":"Pinto","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4805-017 Braga\/Guimar\u00e3es, Portugal"},{"name":"B\u2019nML\u2014Behavioral &Molecular Lab, 4715-057 Braga, 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