Transcription factor NRF2 controls the fate of neural stem cells in the subgranular zone of the hippocampus
Autor(a) principal: | |
---|---|
Data de Publicação: | 2017 |
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/10316/108340 https://doi.org/10.1016/j.redox.2017.06.010 |
Resumo: | Neural stem/progenitor cells (NSPCs) located at the subgranular zone (SGZ) of the hippocampus participate in the maintenance of synaptic networks that ensure cognitive functions during life. Although it is known that this neurogenic niche losses activity with oxidative stress and ageing, the molecular events involved in its regulation are largely unknown. Here, we studied the role of transcription factor Nuclear Factor-Erythroid 2-Related Factor 2 (NRF2) in the control of NSPCs destinies in the SGZ. We first describe that NRF2-knockout (Nrf2-/-) mice exhibit impaired long term potentiation, a function that requires integrity of the SGZ, therefore suggesting a cognitive deficit that might be linked to hippocampal neurogenesis. Then, we found a reduction in NSCs from birth to adulthood that was exacerbated in Nrf2-/- vs. Nrf2+/+ mice. The clonogenic and proliferative capacity of SGZ-derived NSPCs from newborn and 3-month-old Nrf2-/- mice was severely reduced as determined in neurosphere cultures. Nrf2-deficiency also impaired neuronal differentiation both the SGZ, and in neurosphere differentiation assays, leading to an abnormal production of astrocytes and oligodendrocytes vs. neurons. Rescue of Nrf2-/- NSPCs by ectopic expression of NRF2 attenuated the alterations in clonogenic, proliferative and differentiating capacity of hippocampal NSPCs. In turn, knockdown of the NRF2 gene in wild type NSPCs reproduced the data obtained with Nrf2-/- NSPCs. Our findings demonstrate the importance of NRF2 in the maintenance of proper proliferation and differentiation rates of hippocampal NSPCs and suggest that interventions to up-regulate NRF2 might provide a mechanism to preserve the neurogenic functionality of the hippocampus. |
id |
RCAP_f3524c1fed94e156204796c87ef668f8 |
---|---|
oai_identifier_str |
oai:estudogeral.uc.pt:10316/108340 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Transcription factor NRF2 controls the fate of neural stem cells in the subgranular zone of the hippocampusHippocampal neurogenesisAgingNRF2Neural stem cellsSubgranular zoneOxidative stressAnimalsAstrocytesHEK293 CellsHippocampusHumansLong-Term PotentiationMiceMice, Inbred C57BLNeural Stem CellsNeuronsOligodendrogliaNeurogenesisNeural stem/progenitor cells (NSPCs) located at the subgranular zone (SGZ) of the hippocampus participate in the maintenance of synaptic networks that ensure cognitive functions during life. Although it is known that this neurogenic niche losses activity with oxidative stress and ageing, the molecular events involved in its regulation are largely unknown. Here, we studied the role of transcription factor Nuclear Factor-Erythroid 2-Related Factor 2 (NRF2) in the control of NSPCs destinies in the SGZ. We first describe that NRF2-knockout (Nrf2-/-) mice exhibit impaired long term potentiation, a function that requires integrity of the SGZ, therefore suggesting a cognitive deficit that might be linked to hippocampal neurogenesis. Then, we found a reduction in NSCs from birth to adulthood that was exacerbated in Nrf2-/- vs. Nrf2+/+ mice. The clonogenic and proliferative capacity of SGZ-derived NSPCs from newborn and 3-month-old Nrf2-/- mice was severely reduced as determined in neurosphere cultures. Nrf2-deficiency also impaired neuronal differentiation both the SGZ, and in neurosphere differentiation assays, leading to an abnormal production of astrocytes and oligodendrocytes vs. neurons. Rescue of Nrf2-/- NSPCs by ectopic expression of NRF2 attenuated the alterations in clonogenic, proliferative and differentiating capacity of hippocampal NSPCs. In turn, knockdown of the NRF2 gene in wild type NSPCs reproduced the data obtained with Nrf2-/- NSPCs. Our findings demonstrate the importance of NRF2 in the maintenance of proper proliferation and differentiation rates of hippocampal NSPCs and suggest that interventions to up-regulate NRF2 might provide a mechanism to preserve the neurogenic functionality of the hippocampus.Elsevier2017-10info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/108340http://hdl.handle.net/10316/108340https://doi.org/10.1016/j.redox.2017.06.010eng22132317Robledinos-Antón, NataliaRojo, Ana IFerreiro, ElisabeteNúñez, ÁngelKrause, Karl-HeinzJaquet, VincentCuadrado, Antonioinfo: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:RCAAP2023-08-25T08:22:39Zoai:estudogeral.uc.pt:10316/108340Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:24:38.624770Repositório 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 |
Transcription factor NRF2 controls the fate of neural stem cells in the subgranular zone of the hippocampus |
title |
Transcription factor NRF2 controls the fate of neural stem cells in the subgranular zone of the hippocampus |
spellingShingle |
Transcription factor NRF2 controls the fate of neural stem cells in the subgranular zone of the hippocampus Robledinos-Antón, Natalia Hippocampal neurogenesis Aging NRF2 Neural stem cells Subgranular zone Oxidative stress Animals Astrocytes HEK293 Cells Hippocampus Humans Long-Term Potentiation Mice Mice, Inbred C57BL Neural Stem Cells Neurons Oligodendroglia Neurogenesis |
title_short |
Transcription factor NRF2 controls the fate of neural stem cells in the subgranular zone of the hippocampus |
title_full |
Transcription factor NRF2 controls the fate of neural stem cells in the subgranular zone of the hippocampus |
title_fullStr |
Transcription factor NRF2 controls the fate of neural stem cells in the subgranular zone of the hippocampus |
title_full_unstemmed |
Transcription factor NRF2 controls the fate of neural stem cells in the subgranular zone of the hippocampus |
title_sort |
Transcription factor NRF2 controls the fate of neural stem cells in the subgranular zone of the hippocampus |
author |
Robledinos-Antón, Natalia |
author_facet |
Robledinos-Antón, Natalia Rojo, Ana I Ferreiro, Elisabete Núñez, Ángel Krause, Karl-Heinz Jaquet, Vincent Cuadrado, Antonio |
author_role |
author |
author2 |
Rojo, Ana I Ferreiro, Elisabete Núñez, Ángel Krause, Karl-Heinz Jaquet, Vincent Cuadrado, Antonio |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Robledinos-Antón, Natalia Rojo, Ana I Ferreiro, Elisabete Núñez, Ángel Krause, Karl-Heinz Jaquet, Vincent Cuadrado, Antonio |
dc.subject.por.fl_str_mv |
Hippocampal neurogenesis Aging NRF2 Neural stem cells Subgranular zone Oxidative stress Animals Astrocytes HEK293 Cells Hippocampus Humans Long-Term Potentiation Mice Mice, Inbred C57BL Neural Stem Cells Neurons Oligodendroglia Neurogenesis |
topic |
Hippocampal neurogenesis Aging NRF2 Neural stem cells Subgranular zone Oxidative stress Animals Astrocytes HEK293 Cells Hippocampus Humans Long-Term Potentiation Mice Mice, Inbred C57BL Neural Stem Cells Neurons Oligodendroglia Neurogenesis |
description |
Neural stem/progenitor cells (NSPCs) located at the subgranular zone (SGZ) of the hippocampus participate in the maintenance of synaptic networks that ensure cognitive functions during life. Although it is known that this neurogenic niche losses activity with oxidative stress and ageing, the molecular events involved in its regulation are largely unknown. Here, we studied the role of transcription factor Nuclear Factor-Erythroid 2-Related Factor 2 (NRF2) in the control of NSPCs destinies in the SGZ. We first describe that NRF2-knockout (Nrf2-/-) mice exhibit impaired long term potentiation, a function that requires integrity of the SGZ, therefore suggesting a cognitive deficit that might be linked to hippocampal neurogenesis. Then, we found a reduction in NSCs from birth to adulthood that was exacerbated in Nrf2-/- vs. Nrf2+/+ mice. The clonogenic and proliferative capacity of SGZ-derived NSPCs from newborn and 3-month-old Nrf2-/- mice was severely reduced as determined in neurosphere cultures. Nrf2-deficiency also impaired neuronal differentiation both the SGZ, and in neurosphere differentiation assays, leading to an abnormal production of astrocytes and oligodendrocytes vs. neurons. Rescue of Nrf2-/- NSPCs by ectopic expression of NRF2 attenuated the alterations in clonogenic, proliferative and differentiating capacity of hippocampal NSPCs. In turn, knockdown of the NRF2 gene in wild type NSPCs reproduced the data obtained with Nrf2-/- NSPCs. Our findings demonstrate the importance of NRF2 in the maintenance of proper proliferation and differentiation rates of hippocampal NSPCs and suggest that interventions to up-regulate NRF2 might provide a mechanism to preserve the neurogenic functionality of the hippocampus. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-10 |
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/10316/108340 http://hdl.handle.net/10316/108340 https://doi.org/10.1016/j.redox.2017.06.010 |
url |
http://hdl.handle.net/10316/108340 https://doi.org/10.1016/j.redox.2017.06.010 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
22132317 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
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 |
|
_version_ |
1799134130549555200 |