Publicação
The role of Tau protein in the stress-induced changes in adult hippocampal neurogenesis
| Resumo: | Exposure to chronic stressful conditions is suggested to increase susceptibility to brain pathology as it is associated with neuroplastic deficits as well as impaired cognition and mood. Specifically, structural/functional changes of hippocampal formation are shown to contribute to the pathophysiology of different stress-related disorders, e.g. depression, with particular focus on the dentate gyrus (DG), a region of the hippocampus where stress is shown to suppress neurogenesis in the adult brain. Yet, the underlying cellular mechanisms of the stress-driven neurogenic deficits are poorly understood. Our previous studies show that chronic stress triggers hyperphosphorylation and malfunction of the cytoskeletal protein Tau that leads to neuronal atrophy and memory deficits. In addition, Tau hyperphosphorylation has been causally related to neuronal malfunction and diminished neurogenesis in Alzheimer’s disease. Based on the above findings, we hereby aim to clarify the role of Tau on stressdriven suppression of neurogenesis in adult hippocampal neurogenic niche. For that purpose, we have exposed male Tau knockout animals (Tau-KO) and their wildtype littermates (WT) to nine weeks of a chronic unpredictable stress paradigm and evaluated proliferation, differentiation and survival of newlyborn cells in the adult DG as well as their significance in hippocampus-dependent function using molecular, cellular and behavioral analysis. We found that, while chronic stress decreased proliferating cells in the DG of WT animals, this effect on the above population was not found in Tau-KO animals. Moreover, neuroblasts and newly-born neurons were also found to be reduced in stressed WT, but not in Tau-KO animals, suggesting an essential mediation of Tau in the damage of cell proliferation and neuronal differentiation induced by chronic stress. In contrast, newly-born astrocytes were decreased in both WTs and Tau-KOs after stress exposure, indicating that Tau is not necessary for stress-induced reduction in the DG astrocytic pool. Furthermore, chronic stress reduced cascades known to regulate cell survival and proliferation in the DG such as PI3K/GSK3β /β -catenin pathway followed by concomitant reduction in mTOR signaling in WT, but not Tau-KO. The above findings highlight Tau as a crucial mediator of stress-driven neurogenic deficits in adult hippocampus adding to our mechanistic understanding of the cellular cascades that may convey the pathogenic role of chronic stress in the brain and its plasticity. |
|---|---|
| Autores principais: | Dioli, Chrysoula |
| Assunto: | Tau Stress Adult neurogenesis Dentate gyrus mTOR Neurogénese adulta Giro denteado Ciências Médicas |
| Ano: | 2016 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1867438211497721856 |
|---|---|
| author | Dioli, Chrysoula |
| author_facet | Dioli, Chrysoula |
| author_role | author |
| contributor_name_str_mv | Peixoto, João Miguel Seiça Bessa RepositóriUM - Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Dioli, Chrysoula\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Peixoto, João Miguel Seiça Bessa RepositóriUM - Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Dioli, Chrysoula |
| datacite.date.Accepted.fl_str_mv | 2016-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2020-01-01T07:00:20Z |
| datacite.date.embargoed.fl_str_mv | 2020-01-01T07:00:20Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Tau Stress Adult neurogenesis Dentate gyrus mTOR Neurogénese adulta Giro denteado Ciências Médicas |
| datacite.titles.title.fl_str_mv | The role of Tau protein in the stress-induced changes in adult hippocampal neurogenesis A função da proteína Tau nas alterações induzidas pelo estresse na neurogénese adulta do hipocampo |
| dc.contributor.none.fl_str_mv | Peixoto, João Miguel Seiça Bessa RepositóriUM - Universidade do Minho |
| dc.creator.none.fl_str_mv | Dioli, Chrysoula |
| dc.date.Accepted.fl_str_mv | 2016-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2020-01-01T07:00:20Z |
| dc.date.embargoed.fl_str_mv | 2020-01-01T07:00:20Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/46910 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Tau Stress Adult neurogenesis Dentate gyrus mTOR Neurogénese adulta Giro denteado Ciências Médicas |
| dc.title.fl_str_mv | The role of Tau protein in the stress-induced changes in adult hippocampal neurogenesis A função da proteína Tau nas alterações induzidas pelo estresse na neurogénese adulta do hipocampo |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_bdcc |
| description | Exposure to chronic stressful conditions is suggested to increase susceptibility to brain pathology as it is associated with neuroplastic deficits as well as impaired cognition and mood. Specifically, structural/functional changes of hippocampal formation are shown to contribute to the pathophysiology of different stress-related disorders, e.g. depression, with particular focus on the dentate gyrus (DG), a region of the hippocampus where stress is shown to suppress neurogenesis in the adult brain. Yet, the underlying cellular mechanisms of the stress-driven neurogenic deficits are poorly understood. Our previous studies show that chronic stress triggers hyperphosphorylation and malfunction of the cytoskeletal protein Tau that leads to neuronal atrophy and memory deficits. In addition, Tau hyperphosphorylation has been causally related to neuronal malfunction and diminished neurogenesis in Alzheimer’s disease. Based on the above findings, we hereby aim to clarify the role of Tau on stressdriven suppression of neurogenesis in adult hippocampal neurogenic niche. For that purpose, we have exposed male Tau knockout animals (Tau-KO) and their wildtype littermates (WT) to nine weeks of a chronic unpredictable stress paradigm and evaluated proliferation, differentiation and survival of newlyborn cells in the adult DG as well as their significance in hippocampus-dependent function using molecular, cellular and behavioral analysis. We found that, while chronic stress decreased proliferating cells in the DG of WT animals, this effect on the above population was not found in Tau-KO animals. Moreover, neuroblasts and newly-born neurons were also found to be reduced in stressed WT, but not in Tau-KO animals, suggesting an essential mediation of Tau in the damage of cell proliferation and neuronal differentiation induced by chronic stress. In contrast, newly-born astrocytes were decreased in both WTs and Tau-KOs after stress exposure, indicating that Tau is not necessary for stress-induced reduction in the DG astrocytic pool. Furthermore, chronic stress reduced cascades known to regulate cell survival and proliferation in the DG such as PI3K/GSK3β /β -catenin pathway followed by concomitant reduction in mTOR signaling in WT, but not Tau-KO. The above findings highlight Tau as a crucial mediator of stress-driven neurogenic deficits in adult hippocampus adding to our mechanistic understanding of the cellular cascades that may convey the pathogenic role of chronic stress in the brain and its plasticity. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | masterThesis |
| fulltext.url.fl_str_mv | https://repositorium.uminho.pt/bitstreams/10477e66-b859-4b7f-9111-a794696b6d73/download |
| id | rum_9e48ef554abb0dc8a6dc48be267ee9ff |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/46910 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/46910 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Dioli, Chrysoula |
| publishDate | 2016 |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engporExposure to chronic stressful conditions is suggested to increase susceptibility to brain pathology as it is associated with neuroplastic deficits as well as impaired cognition and mood. Specifically, structural/functional changes of hippocampal formation are shown to contribute to the pathophysiology of different stress-related disorders, e.g. depression, with particular focus on the dentate gyrus (DG), a region of the hippocampus where stress is shown to suppress neurogenesis in the adult brain. Yet, the underlying cellular mechanisms of the stress-driven neurogenic deficits are poorly understood. Our previous studies show that chronic stress triggers hyperphosphorylation and malfunction of the cytoskeletal protein Tau that leads to neuronal atrophy and memory deficits. In addition, Tau hyperphosphorylation has been causally related to neuronal malfunction and diminished neurogenesis in Alzheimer’s disease. Based on the above findings, we hereby aim to clarify the role of Tau on stressdriven suppression of neurogenesis in adult hippocampal neurogenic niche. For that purpose, we have exposed male Tau knockout animals (Tau-KO) and their wildtype littermates (WT) to nine weeks of a chronic unpredictable stress paradigm and evaluated proliferation, differentiation and survival of newlyborn cells in the adult DG as well as their significance in hippocampus-dependent function using molecular, cellular and behavioral analysis. We found that, while chronic stress decreased proliferating cells in the DG of WT animals, this effect on the above population was not found in Tau-KO animals. Moreover, neuroblasts and newly-born neurons were also found to be reduced in stressed WT, but not in Tau-KO animals, suggesting an essential mediation of Tau in the damage of cell proliferation and neuronal differentiation induced by chronic stress. In contrast, newly-born astrocytes were decreased in both WTs and Tau-KOs after stress exposure, indicating that Tau is not necessary for stress-induced reduction in the DG astrocytic pool. Furthermore, chronic stress reduced cascades known to regulate cell survival and proliferation in the DG such as PI3K/GSK3β /β -catenin pathway followed by concomitant reduction in mTOR signaling in WT, but not Tau-KO. The above findings highlight Tau as a crucial mediator of stress-driven neurogenic deficits in adult hippocampus adding to our mechanistic understanding of the cellular cascades that may convey the pathogenic role of chronic stress in the brain and its plasticity.application/pdfporThe role of Tau protein in the stress-induced changes in adult hippocampal neurogenesisAlternativeTitleporA função da proteína Tau nas alterações induzidas pelo estresse na neurogénese adulta do hipocampoDioli, ChrysoulaPeixoto, João Miguel Seiça BessaHostingInstitutionOrganizationalRepositóriUM - Universidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptTID2014831062020-01-01T07:00:20Z201620162016-01-01T00:00:00ZHandlehttps://hdl.handle.net/1822/46910http://purl.org/coar/access_right/c_abf2open accessTauStressAdult neurogenesisDentate gyrusmTORNeurogénese adultaGiro denteadohttp://www.oecd.org/science/inno/38235147.pdfFields of Science and Technology (FOS)Ciências Médicas4185527 bytesliteraturehttp://purl.org/coar/resource_type/c_bdccmaster thesishttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorium.uminho.pt/bitstreams/10477e66-b859-4b7f-9111-a794696b6d73/download |
| spellingShingle | The role of Tau protein in the stress-induced changes in adult hippocampal neurogenesis Dioli, Chrysoula Tau Stress Adult neurogenesis Dentate gyrus mTOR Neurogénese adulta Giro denteado Ciências Médicas |
| status | SINGLETON |
| subject.fl_str_mv | Tau Stress Adult neurogenesis Dentate gyrus mTOR Neurogénese adulta Giro denteado |
| subject.other.fl_str_mv | Ciências Médicas |
| title | The role of Tau protein in the stress-induced changes in adult hippocampal neurogenesis |
| title_full | The role of Tau protein in the stress-induced changes in adult hippocampal neurogenesis |
| title_fullStr | The role of Tau protein in the stress-induced changes in adult hippocampal neurogenesis |
| title_full_unstemmed | The role of Tau protein in the stress-induced changes in adult hippocampal neurogenesis |
| title_short | The role of Tau protein in the stress-induced changes in adult hippocampal neurogenesis |
| title_sort | The role of Tau protein in the stress-induced changes in adult hippocampal neurogenesis |
| topic | Tau Stress Adult neurogenesis Dentate gyrus mTOR Neurogénese adulta Giro denteado Ciências Médicas |
| topic_facet | Tau Stress Adult neurogenesis Dentate gyrus mTOR Neurogénese adulta Giro denteado Ciências Médicas |
| url | https://hdl.handle.net/1822/46910 |
| visible | 1 |