The mitochondrial antioxidant Sirtuin3 cooperates with lipid metabolism to safeguard neurogenesis in aging and depression

Detalhes bibliográficos
Autor(a) principal: Santos, Sónia Sá
Data de Publicação: 2021
Outros Autores: Moreira, João B., Costa, Márcia, Rodrigues, Rui S., Sebastião, Ana M, Xapelli, Sara, Solá, Susana
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/59502
Resumo: Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
id RCAP_6fa4d7e9a86205b92c226b161e34b0de
oai_identifier_str oai:repositorio.ul.pt:10451/59502
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling The mitochondrial antioxidant Sirtuin3 cooperates with lipid metabolism to safeguard neurogenesis in aging and depressionSIRT3AgingDepressionLipid metabolismMitochondriaNeural stem cellsCopyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).Neural stem cells (NSCs), crucial for memory in the adult brain, are also pivotal to buffer depressive behavior. However, the mechanisms underlying the boost in NSC activity throughout life are still largely undiscovered. Here, we aimed to explore the role of deacetylase Sirtuin 3 (SIRT3), a central player in mitochondrial metabolism and oxidative protection, in the fate of NSC under aging and depression-like contexts. We showed that chronic treatment with tert-butyl hydroperoxide induces NSC aging, markedly reducing SIRT3 protein. SIRT3 overexpression, in turn, restored mitochondrial oxidative stress and the differentiation potential of aged NSCs. Notably, SIRT3 was also shown to physically interact with the long chain acyl-CoA dehydrogenase (LCAD) in NSCs and to require its activation to prevent age-impaired neurogenesis. Finally, the SIRT3 regulatory network was investigated in vivo using the unpredictable chronic mild stress (uCMS) paradigm to mimic depressive-like behavior in mice. Interestingly, uCMS mice presented lower levels of neurogenesis and LCAD expression in the same neurogenic niches, being significantly rescued by physical exercise, a well-known upregulator of SIRT3 and lipid metabolism. Our results suggest that targeting NSC metabolism, namely through SIRT3, might be a suitable promising strategy to delay NSC aging and confer stress resilience.This work was supported by grants PTDC/MED-NEU/29650/2017, UIDB/04138/2020 and UIDP/04138/2020 from Fundação para a Ciência e a Tecnologia, Lisboa, Portugal.MDPIRepositório da Universidade de LisboaSantos, Sónia SáMoreira, João B.Costa, MárciaRodrigues, Rui S.Sebastião, Ana MXapelli, SaraSolá, Susana2023-09-28T16:04:31Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/59502engCells. 2021 Dec 29;11(1):9010.3390/cells110100902073-4409info: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:RCAAP2024-11-20T18:23:49Zoai:repositorio.ul.pt:10451/59502Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-11-20T18:23:49Repositório 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 The mitochondrial antioxidant Sirtuin3 cooperates with lipid metabolism to safeguard neurogenesis in aging and depression
title The mitochondrial antioxidant Sirtuin3 cooperates with lipid metabolism to safeguard neurogenesis in aging and depression
spellingShingle The mitochondrial antioxidant Sirtuin3 cooperates with lipid metabolism to safeguard neurogenesis in aging and depression
Santos, Sónia Sá
SIRT3
Aging
Depression
Lipid metabolism
Mitochondria
Neural stem cells
title_short The mitochondrial antioxidant Sirtuin3 cooperates with lipid metabolism to safeguard neurogenesis in aging and depression
title_full The mitochondrial antioxidant Sirtuin3 cooperates with lipid metabolism to safeguard neurogenesis in aging and depression
title_fullStr The mitochondrial antioxidant Sirtuin3 cooperates with lipid metabolism to safeguard neurogenesis in aging and depression
title_full_unstemmed The mitochondrial antioxidant Sirtuin3 cooperates with lipid metabolism to safeguard neurogenesis in aging and depression
title_sort The mitochondrial antioxidant Sirtuin3 cooperates with lipid metabolism to safeguard neurogenesis in aging and depression
author Santos, Sónia Sá
author_facet Santos, Sónia Sá
Moreira, João B.
Costa, Márcia
Rodrigues, Rui S.
Sebastião, Ana M
Xapelli, Sara
Solá, Susana
author_role author
author2 Moreira, João B.
Costa, Márcia
Rodrigues, Rui S.
Sebastião, Ana M
Xapelli, Sara
Solá, Susana
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Santos, Sónia Sá
Moreira, João B.
Costa, Márcia
Rodrigues, Rui S.
Sebastião, Ana M
Xapelli, Sara
Solá, Susana
dc.subject.por.fl_str_mv SIRT3
Aging
Depression
Lipid metabolism
Mitochondria
Neural stem cells
topic SIRT3
Aging
Depression
Lipid metabolism
Mitochondria
Neural stem cells
description Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01T00:00:00Z
2023-09-28T16:04:31Z
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/10451/59502
url http://hdl.handle.net/10451/59502
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Cells. 2021 Dec 29;11(1):90
10.3390/cells11010090
2073-4409
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 MDPI
publisher.none.fl_str_mv 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 mluisa.alvim@gmail.com
_version_ 1817549250727247872

Registros relacionados