Differential and converging molecular mechanisms of antidepressants' action in the hippocampal dentate gyrus
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/32923 |
Resumo: | Major depression is a highly prevalent, multidimensional disorder. Although several classes of antidepressants (ADs) are currently available, treatment efficacy is limited, and relapse rates are high; thus, there is a need to find better therapeutic strategies. Neuroplastic changes in brain regions such as the hippocampal dentate gyrus (DG) accompany depression and its amelioration with ADs. In this study, the unpredictable chronic mild stress (uCMS) rat model of depression was used to determine the molecular mediators of chronic stress and the targets of four ADs with different pharmacological profiles (fluoxetine, imipramine, tianeptine, and agomelatine) in the hippocampal DG. All ADs, except agomelatine, reversed the depression-like behavior and neuroplastic changes produced by uCMS. Chronic stress induced significant molecular changes that were generally reversed by fluoxetine, imipramine, and tianeptine. Fluoxetine primarily acted on neurons to reduce the expression of pro-inflammatory response genes and increased a set of genes involved in cell metabolism. Similarities were found between the molecular actions and targets of imipramine and tianeptine that activated pathways related to cellular protection. Agomelatine presented a unique profile, with pronounced effects on genes related to Rho-GTPase-related pathways in oligodendrocytes and neurons. These differential molecular signatures of ADs studied contribute to our understanding of the processes implicated in the onset and treatment of depression-like symptoms. |
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Differential and converging molecular mechanisms of antidepressants' action in the hippocampal dentate gyrusScience & TechnologyMajor depression is a highly prevalent, multidimensional disorder. Although several classes of antidepressants (ADs) are currently available, treatment efficacy is limited, and relapse rates are high; thus, there is a need to find better therapeutic strategies. Neuroplastic changes in brain regions such as the hippocampal dentate gyrus (DG) accompany depression and its amelioration with ADs. In this study, the unpredictable chronic mild stress (uCMS) rat model of depression was used to determine the molecular mediators of chronic stress and the targets of four ADs with different pharmacological profiles (fluoxetine, imipramine, tianeptine, and agomelatine) in the hippocampal DG. All ADs, except agomelatine, reversed the depression-like behavior and neuroplastic changes produced by uCMS. Chronic stress induced significant molecular changes that were generally reversed by fluoxetine, imipramine, and tianeptine. Fluoxetine primarily acted on neurons to reduce the expression of pro-inflammatory response genes and increased a set of genes involved in cell metabolism. Similarities were found between the molecular actions and targets of imipramine and tianeptine that activated pathways related to cellular protection. Agomelatine presented a unique profile, with pronounced effects on genes related to Rho-GTPase-related pathways in oligodendrocytes and neurons. These differential molecular signatures of ADs studied contribute to our understanding of the processes implicated in the onset and treatment of depression-like symptoms.Patricia Patricio, Antonio Mateus-Pinheiro, Monica Morais, and Nuno Dinis Alves received fellowships from the Portuguese Foundation for Science and Technology (FCT). Michal Korostynski and Marcin Piechota were funded by the POIG De-Me-Ter 3.1 and NCN 2011/03/D/NZ3/01686 grants. This study was co-funded by the Life and Health Sciences Research Institute (ICVS) and ON. 2-O NOVO NORTE-North Portugal Regional Operational Programme 2007/2013, of the National Strategic Reference Framework (NSRF) 2007/ 2013, through the European Regional Development Fund (ERDF) and by the SwitchBox Consortium (Contract FP7-Health-F2-2010-259772 from the European Union). The authors declare no conflict of interest.Palgrave MacmillanUniversidade do MinhoPatrício, P.Pinheiro, António MateusIrmler, MartinAlves, Nuno D.Santos, Ana R. MachadoMorais, MónicaSilva-Correia, JoanaKorostynski, MichalPiechota, MarcinStoffel, RainerBeckers, JohannesBessa, J. M.Almeida, O. F. X.Sousa, NunoPinto, Luísa20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/32923engPatricio, P., Mateus-Pinheiro, A., Irmler, M., Alves, N. D., Machado-Santos, A. R., Morais, M., . . . Pinto, L. (2015). Differential and Converging Molecular Mechanisms of Antidepressants' Action in the Hippocampal Dentate Gyrus. Neuropsychopharmacology, 40(2), 338-349. doi: 10.1038/npp.2014.1760893-133X10.1038/npp.2014.17625035085http://www.nature.cominfo: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:RCAAP2023-07-21T12:27:52Zoai:repositorium.sdum.uminho.pt:1822/32923Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:22:33.597754Repositório 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 |
Differential and converging molecular mechanisms of antidepressants' action in the hippocampal dentate gyrus |
title |
Differential and converging molecular mechanisms of antidepressants' action in the hippocampal dentate gyrus |
spellingShingle |
Differential and converging molecular mechanisms of antidepressants' action in the hippocampal dentate gyrus Patrício, P. Science & Technology |
title_short |
Differential and converging molecular mechanisms of antidepressants' action in the hippocampal dentate gyrus |
title_full |
Differential and converging molecular mechanisms of antidepressants' action in the hippocampal dentate gyrus |
title_fullStr |
Differential and converging molecular mechanisms of antidepressants' action in the hippocampal dentate gyrus |
title_full_unstemmed |
Differential and converging molecular mechanisms of antidepressants' action in the hippocampal dentate gyrus |
title_sort |
Differential and converging molecular mechanisms of antidepressants' action in the hippocampal dentate gyrus |
author |
Patrício, P. |
author_facet |
Patrício, P. Pinheiro, António Mateus Irmler, Martin Alves, Nuno D. Santos, Ana R. Machado Morais, Mónica Silva-Correia, Joana Korostynski, Michal Piechota, Marcin Stoffel, Rainer Beckers, Johannes Bessa, J. M. Almeida, O. F. X. Sousa, Nuno Pinto, Luísa |
author_role |
author |
author2 |
Pinheiro, António Mateus Irmler, Martin Alves, Nuno D. Santos, Ana R. Machado Morais, Mónica Silva-Correia, Joana Korostynski, Michal Piechota, Marcin Stoffel, Rainer Beckers, Johannes Bessa, J. M. Almeida, O. F. X. Sousa, Nuno Pinto, Luísa |
author2_role |
author author author author author 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, P. Pinheiro, António Mateus Irmler, Martin Alves, Nuno D. Santos, Ana R. Machado Morais, Mónica Silva-Correia, Joana Korostynski, Michal Piechota, Marcin Stoffel, Rainer Beckers, Johannes Bessa, J. M. Almeida, O. F. X. Sousa, Nuno Pinto, Luísa |
dc.subject.por.fl_str_mv |
Science & Technology |
topic |
Science & Technology |
description |
Major depression is a highly prevalent, multidimensional disorder. Although several classes of antidepressants (ADs) are currently available, treatment efficacy is limited, and relapse rates are high; thus, there is a need to find better therapeutic strategies. Neuroplastic changes in brain regions such as the hippocampal dentate gyrus (DG) accompany depression and its amelioration with ADs. In this study, the unpredictable chronic mild stress (uCMS) rat model of depression was used to determine the molecular mediators of chronic stress and the targets of four ADs with different pharmacological profiles (fluoxetine, imipramine, tianeptine, and agomelatine) in the hippocampal DG. All ADs, except agomelatine, reversed the depression-like behavior and neuroplastic changes produced by uCMS. Chronic stress induced significant molecular changes that were generally reversed by fluoxetine, imipramine, and tianeptine. Fluoxetine primarily acted on neurons to reduce the expression of pro-inflammatory response genes and increased a set of genes involved in cell metabolism. Similarities were found between the molecular actions and targets of imipramine and tianeptine that activated pathways related to cellular protection. Agomelatine presented a unique profile, with pronounced effects on genes related to Rho-GTPase-related pathways in oligodendrocytes and neurons. These differential molecular signatures of ADs studied contribute to our understanding of the processes implicated in the onset and treatment of depression-like symptoms. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015 2015-01-01T00:00:00Z |
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 |
http://hdl.handle.net/1822/32923 |
url |
http://hdl.handle.net/1822/32923 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Patricio, P., Mateus-Pinheiro, A., Irmler, M., Alves, N. D., Machado-Santos, A. R., Morais, M., . . . Pinto, L. (2015). Differential and Converging Molecular Mechanisms of Antidepressants' Action in the Hippocampal Dentate Gyrus. Neuropsychopharmacology, 40(2), 338-349. doi: 10.1038/npp.2014.176 0893-133X 10.1038/npp.2014.176 25035085 http://www.nature.com |
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 |
Palgrave Macmillan |
publisher.none.fl_str_mv |
Palgrave Macmillan |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132695980146688 |