Beyond new neurons in the adult hippocampus: imipramine acts as a pro-astrogliogenic factor and rescues cognitive impairments induced by stress exposure
Autor(a) principal: | |
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Data de Publicação: | 2022 |
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/1822/78355 |
Resumo: | Depression is a prevalent, socially burdensome disease. Different studies have demonstrated the important role of astrocytes in the pathophysiology of depression as modulators of neurotransmission and neurovascular coupling. This is evidenced by astrocyte impairments observed in brains of depressed patients and the appearance of depressive-like behaviors upon astrocytic dysfunctions in animal models. However, little is known about the importance of de novo generated astrocytes in the mammalian brain and in particular its possible involvement in the precipitation of depression and in the therapeutic actions of current antidepressants (ADs). Therefore, we studied the modulation of astrocytes and adult astrogliogenesis in the hippocampal dentate gyrus (DG) of rats exposed to an unpredictable chronic mild stress (uCMS) protocol, untreated and treated for two weeks with antidepressants—fluoxetine and imipramine. Our results show that adult astrogliogenesis in the DG is modulated by stress and imipramine. This study reveals that distinct classes of ADs impact differently in the astrogliogenic process, showing different cellular mechanisms relevant to the recovery from behavioral deficits induced by chronic stress exposure. As such, in addition to those resident, the newborn astrocytes in the hippocampal DG might also be promising therapeutic targets for future therapies in the neuropsychiatric field. |
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Beyond new neurons in the adult hippocampus: imipramine acts as a pro-astrogliogenic factor and rescues cognitive impairments induced by stress exposureAstrocytesHippocampusDentate gyrusAstrogliogenesisChronic stressAntidepressantsScience & TechnologyDepression is a prevalent, socially burdensome disease. Different studies have demonstrated the important role of astrocytes in the pathophysiology of depression as modulators of neurotransmission and neurovascular coupling. This is evidenced by astrocyte impairments observed in brains of depressed patients and the appearance of depressive-like behaviors upon astrocytic dysfunctions in animal models. However, little is known about the importance of de novo generated astrocytes in the mammalian brain and in particular its possible involvement in the precipitation of depression and in the therapeutic actions of current antidepressants (ADs). Therefore, we studied the modulation of astrocytes and adult astrogliogenesis in the hippocampal dentate gyrus (DG) of rats exposed to an unpredictable chronic mild stress (uCMS) protocol, untreated and treated for two weeks with antidepressants—fluoxetine and imipramine. Our results show that adult astrogliogenesis in the DG is modulated by stress and imipramine. This study reveals that distinct classes of ADs impact differently in the astrogliogenic process, showing different cellular mechanisms relevant to the recovery from behavioral deficits induced by chronic stress exposure. As such, in addition to those resident, the newborn astrocytes in the hippocampal DG might also be promising therapeutic targets for future therapies in the neuropsychiatric field.ARMS: ELC, NDA, PP, AMP, JSC, MM, AJR, JFO, and L.P. received fellowships from the Portuguese Foundation for Science and Technology (FCT) (IF/00328/2015 to J.F.O.; 2020.02855.CEECIND to LP). This work was funded by FCT (IF/01079/2014, PTDC/MED-NEU/31417/2017 Grant to JFO), BIAL Foundation Grants (037/18 to J.F.O. and 427/14 to L.P.), “la Caixa” Foundation Health Research Grant (LCF/PR/HR21/52410024) and Nature Research Award for Driving Global Impact—2019 Brain Sciences (to L.P.). This was also co-funded by the Life and Health Sciences Research Institute (ICVS), and by FEDER, through the Competitiveness Internationalization Operational Program (POCI), and by National funds, through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020. Moreover, this work has been funded by ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI—Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122; by National funds, through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020; “la Caixa” Foundation (ID 100010434 to A.J.R.), under the agreement LCF/PR/HR20/52400020; and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 101003187 to A.J.R.).Multidisciplinary Digital Publishing Institute (MDPI)Universidade do MinhoMachado-Santos, Ana R.Loureiro-Campos, EduardoPatrício, PatríciaAraújo, Bruna Alexandra ValeAlves, Nuno DinisMateus-Pinheiro, AntónioCorreia, Joana Sofia SilvaMorais, MónicaPeixoto, João Miguel Seiça BessaSousa, NunoRodrigues, Ana JoãoOliveira, João F.Pinto, Luísa2022-01-242022-01-24T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/78355engMachado-Santos, A.R.; Loureiro-Campos, E.; Patrício, P.; Araújo, B.; Alves, N.D.; Mateus-Pinheiro, A.; Correia, J.S.; Morais, M.; Bessa, J.M.; Sousa, N.; Rodrigues, A.J.; Oliveira, J.F.; Pinto, L. Beyond New Neurons in the Adult Hippocampus: Imipramine Acts as a Pro-Astrogliogenic Factor and Rescues Cognitive Impairments Induced by Stress Exposure. Cells 2022, 11, 390. https://doi.org/10.3390/cells110303902073-440910.3390/cells1103039035159199390https://www.mdpi.com/2073-4409/11/3/390info: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:RCAAP2023-07-21T11:54:51Zoai:repositorium.sdum.uminho.pt:1822/78355Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:44:19.173946Repositório 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 |
Beyond new neurons in the adult hippocampus: imipramine acts as a pro-astrogliogenic factor and rescues cognitive impairments induced by stress exposure |
title |
Beyond new neurons in the adult hippocampus: imipramine acts as a pro-astrogliogenic factor and rescues cognitive impairments induced by stress exposure |
spellingShingle |
Beyond new neurons in the adult hippocampus: imipramine acts as a pro-astrogliogenic factor and rescues cognitive impairments induced by stress exposure Machado-Santos, Ana R. Astrocytes Hippocampus Dentate gyrus Astrogliogenesis Chronic stress Antidepressants Science & Technology |
title_short |
Beyond new neurons in the adult hippocampus: imipramine acts as a pro-astrogliogenic factor and rescues cognitive impairments induced by stress exposure |
title_full |
Beyond new neurons in the adult hippocampus: imipramine acts as a pro-astrogliogenic factor and rescues cognitive impairments induced by stress exposure |
title_fullStr |
Beyond new neurons in the adult hippocampus: imipramine acts as a pro-astrogliogenic factor and rescues cognitive impairments induced by stress exposure |
title_full_unstemmed |
Beyond new neurons in the adult hippocampus: imipramine acts as a pro-astrogliogenic factor and rescues cognitive impairments induced by stress exposure |
title_sort |
Beyond new neurons in the adult hippocampus: imipramine acts as a pro-astrogliogenic factor and rescues cognitive impairments induced by stress exposure |
author |
Machado-Santos, Ana R. |
author_facet |
Machado-Santos, Ana R. Loureiro-Campos, Eduardo Patrício, Patrícia Araújo, Bruna Alexandra Vale Alves, Nuno Dinis Mateus-Pinheiro, António Correia, Joana Sofia Silva Morais, Mónica Peixoto, João Miguel Seiça Bessa Sousa, Nuno Rodrigues, Ana João Oliveira, João F. Pinto, Luísa |
author_role |
author |
author2 |
Loureiro-Campos, Eduardo Patrício, Patrícia Araújo, Bruna Alexandra Vale Alves, Nuno Dinis Mateus-Pinheiro, António Correia, Joana Sofia Silva Morais, Mónica Peixoto, João Miguel Seiça Bessa Sousa, Nuno Rodrigues, Ana João Oliveira, João F. Pinto, Luísa |
author2_role |
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 |
Machado-Santos, Ana R. Loureiro-Campos, Eduardo Patrício, Patrícia Araújo, Bruna Alexandra Vale Alves, Nuno Dinis Mateus-Pinheiro, António Correia, Joana Sofia Silva Morais, Mónica Peixoto, João Miguel Seiça Bessa Sousa, Nuno Rodrigues, Ana João Oliveira, João F. Pinto, Luísa |
dc.subject.por.fl_str_mv |
Astrocytes Hippocampus Dentate gyrus Astrogliogenesis Chronic stress Antidepressants Science & Technology |
topic |
Astrocytes Hippocampus Dentate gyrus Astrogliogenesis Chronic stress Antidepressants Science & Technology |
description |
Depression is a prevalent, socially burdensome disease. Different studies have demonstrated the important role of astrocytes in the pathophysiology of depression as modulators of neurotransmission and neurovascular coupling. This is evidenced by astrocyte impairments observed in brains of depressed patients and the appearance of depressive-like behaviors upon astrocytic dysfunctions in animal models. However, little is known about the importance of de novo generated astrocytes in the mammalian brain and in particular its possible involvement in the precipitation of depression and in the therapeutic actions of current antidepressants (ADs). Therefore, we studied the modulation of astrocytes and adult astrogliogenesis in the hippocampal dentate gyrus (DG) of rats exposed to an unpredictable chronic mild stress (uCMS) protocol, untreated and treated for two weeks with antidepressants—fluoxetine and imipramine. Our results show that adult astrogliogenesis in the DG is modulated by stress and imipramine. This study reveals that distinct classes of ADs impact differently in the astrogliogenic process, showing different cellular mechanisms relevant to the recovery from behavioral deficits induced by chronic stress exposure. As such, in addition to those resident, the newborn astrocytes in the hippocampal DG might also be promising therapeutic targets for future therapies in the neuropsychiatric field. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-01-24 2022-01-24T00:00:00Z |
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/1822/78355 |
url |
https://hdl.handle.net/1822/78355 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Machado-Santos, A.R.; Loureiro-Campos, E.; Patrício, P.; Araújo, B.; Alves, N.D.; Mateus-Pinheiro, A.; Correia, J.S.; Morais, M.; Bessa, J.M.; Sousa, N.; Rodrigues, A.J.; Oliveira, J.F.; Pinto, L. Beyond New Neurons in the Adult Hippocampus: Imipramine Acts as a Pro-Astrogliogenic Factor and Rescues Cognitive Impairments Induced by Stress Exposure. Cells 2022, 11, 390. https://doi.org/10.3390/cells11030390 2073-4409 10.3390/cells11030390 35159199 390 https://www.mdpi.com/2073-4409/11/3/390 |
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 |
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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 |
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 |
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1799132191952732160 |