Beyond new neurons in the adult hippocampus: imipramine acts as a pro-astrogliogenic factor and rescues cognitive impairments induced by stress exposure

Detalhes bibliográficos
Autor(a) principal: Machado-Santos, Ana R.
Data de Publicação: 2022
Outros Autores: 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
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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spelling 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)
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