Cell cycle regulation of hippocampal progenitor cells in experimental models of depression and after treatment with fluoxetine
Autor(a) principal: | |
---|---|
Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/1822/75842 |
Resumo: | 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 <i>in vivo</i> unpredictable chronic mild stress (uCMS) rat model of depression and <i>in vitro</i> 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. <i>In vitro</i>, 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. |
id |
RCAP_6c39357f12d8ff72bb25d650563e7581 |
---|---|
oai_identifier_str |
oai:repositorium.sdum.uminho.pt:1822/75842 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Cell cycle regulation of hippocampal progenitor cells in experimental models of depression and after treatment with fluoxetineUnpredictable chronic mild stressDepressionAntidepressantsHippocampal cytogenesisCell cycleScience & TechnologyChanges 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 <i>in vivo</i> unpredictable chronic mild stress (uCMS) rat model of depression and <i>in vitro</i> 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. <i>In vitro</i>, 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.This research was funded by FCT (grant number IF/01079/2014 and 2020.02855.CEECIND to LP) and the Nature Research Award for Driving Global Impact-2019 Brain Sciences (to LP); the Life and Health Sciences Research Institute (ICVS); FEDER, through the Competitiveness Internationalization Operational Program (POCI); National funds through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020; the projects NORTE-01- 0145-FEDER-000013 and NORTE-01-0145-FEDER-000023.; the ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI—Portuguese Platform of Bioimaging (PPBI-POCI-01-0145- FEDER-022122); National funds through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020. Part of this work was also funded by “la Caixa” Foundation (ID 100010434), under the agreement LCF/PR/HR20/52400020; and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 101003187).Multidisciplinary Digital Publishing Institute (MDPI)Universidade do MinhoPatrício, PatríciaMateus-Pinheiro, AntónioMachado-Santos, Ana RitaAlves, Nuno Dinis Lopes OliveiraCorreia, Joana Sofia SilvaMorais, MónicaPeixoto, João Miguel Seiça BessaRodrigues, Ana JoãoSousa, NunoPinto, Luísa2021-10-302021-10-30T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/75842engPatrício, P.; Mateus-Pinheiro, A.; Machado-Santos, A.R.; Alves, N.D.; Correia, J.S.; Morais, M.; Bessa, J.M.; Rodrigues, A.J.; Sousa, N.; Pinto, L. Cell Cycle Regulation of Hippocampal Progenitor Cells in Experimental Models of Depression and after Treatment with Fluoxetine. Int. J. Mol. Sci. 2021, 22, 11798. https://doi.org/10.3390/ijms2221117981661-65961422-006710.3390/ijms2221117983476923211798https://www.mdpi.com/1422-0067/22/21/11798info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:39:32Zoai:repositorium.sdum.uminho.pt:1822/75842Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:36:10.228628Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Cell cycle regulation of hippocampal progenitor cells in experimental models of depression and after treatment with fluoxetine |
title |
Cell cycle regulation of hippocampal progenitor cells in experimental models of depression and after treatment with fluoxetine |
spellingShingle |
Cell cycle regulation of hippocampal progenitor cells in experimental models of depression and after treatment with fluoxetine Patrício, Patrícia Unpredictable chronic mild stress Depression Antidepressants Hippocampal cytogenesis Cell cycle Science & Technology |
title_short |
Cell cycle regulation of hippocampal progenitor cells in experimental models of depression and after treatment with fluoxetine |
title_full |
Cell cycle regulation of hippocampal progenitor cells in experimental models of depression and after treatment with fluoxetine |
title_fullStr |
Cell cycle regulation of hippocampal progenitor cells in experimental models of depression and after treatment with fluoxetine |
title_full_unstemmed |
Cell cycle regulation of hippocampal progenitor cells in experimental models of depression and after treatment with fluoxetine |
title_sort |
Cell cycle regulation of hippocampal progenitor cells in experimental models of depression and after treatment with fluoxetine |
author |
Patrício, Patrícia |
author_facet |
Patrício, Patrícia Mateus-Pinheiro, António Machado-Santos, Ana Rita Alves, Nuno Dinis Lopes Oliveira Correia, Joana Sofia Silva Morais, Mónica Peixoto, João Miguel Seiça Bessa Rodrigues, Ana João Sousa, Nuno Pinto, Luísa |
author_role |
author |
author2 |
Mateus-Pinheiro, António Machado-Santos, Ana Rita Alves, Nuno Dinis Lopes Oliveira Correia, Joana Sofia Silva Morais, Mónica Peixoto, João Miguel Seiça Bessa Rodrigues, Ana João Sousa, Nuno Pinto, Luísa |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Patrício, Patrícia Mateus-Pinheiro, António Machado-Santos, Ana Rita Alves, Nuno Dinis Lopes Oliveira Correia, Joana Sofia Silva Morais, Mónica Peixoto, João Miguel Seiça Bessa Rodrigues, Ana João Sousa, Nuno Pinto, Luísa |
dc.subject.por.fl_str_mv |
Unpredictable chronic mild stress Depression Antidepressants Hippocampal cytogenesis Cell cycle Science & Technology |
topic |
Unpredictable chronic mild stress Depression Antidepressants Hippocampal cytogenesis Cell cycle Science & Technology |
description |
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 <i>in vivo</i> unpredictable chronic mild stress (uCMS) rat model of depression and <i>in vitro</i> 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. <i>In vitro</i>, 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. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-10-30 2021-10-30T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/1822/75842 |
url |
https://hdl.handle.net/1822/75842 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Patrício, P.; Mateus-Pinheiro, A.; Machado-Santos, A.R.; Alves, N.D.; Correia, J.S.; Morais, M.; Bessa, J.M.; Rodrigues, A.J.; Sousa, N.; Pinto, L. Cell Cycle Regulation of Hippocampal Progenitor Cells in Experimental Models of Depression and after Treatment with Fluoxetine. Int. J. Mol. Sci. 2021, 22, 11798. https://doi.org/10.3390/ijms222111798 1661-6596 1422-0067 10.3390/ijms222111798 34769232 11798 https://www.mdpi.com/1422-0067/22/21/11798 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799132889679396864 |