AP2γ controls adult hippocampal neurogenesis and modulates cognitive, but not anxiety or depressive-like behavior
Autor(a) principal: | |
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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: | https://hdl.handle.net/1822/49593 |
Resumo: | Hippocampal neurogenesis has been proposed to participate in a myriad of behavioral responses, both in basal states and in the context of neuropsychiatric disorders. Here, we identify activating protein 2γ 3 (AP2γ 3, also known as Tcfap2c), originally described to regulate the generation of neurons in the developing cortex, as a modulator of adult hippocampal glutamatergic neurogenesis in mice. Specifically, AP2γ 3 is present in a sub-population of hippocampal transient amplifying progenitors. There, it is found to act as a positive regulator of the cell fate determinants Tbr2 and NeuroD, promoting proliferation and differentiation of new glutamatergic granular neurons. Conditional ablation of AP2γ 3 in the adult brain significantly reduced hippocampal neurogenesis and disrupted neural coherence between the ventral hippocampus and the medial prefrontal cortex. Furthermore, it resulted in the precipitation of multimodal cognitive deficits. This indicates that the sub-population of AP2γ 3-positive hippocampal progenitors may constitute an important cellular substrate for hippocampal-dependent cognitive functions. Concurrently, AP2γ 3 deletion produced significant impairments in contextual memory and reversal learning. More so, in a water maze reference memory task a delay in the transition to cognitive strategies relying on hippocampal function integrity was observed. Interestingly, anxiety- and d epressive-like behaviors were not significantly affected. Altogether, findings open new perspectives in understanding the role of specific sub-populations of newborn neurons in the (patho)physiology of neuropsychiatric disorders affecting hippocampal neuroplasticity and cognitive function in the adult brain. |
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AP2γ controls adult hippocampal neurogenesis and modulates cognitive, but not anxiety or depressive-like behaviorScience & TechnologyHippocampal neurogenesis has been proposed to participate in a myriad of behavioral responses, both in basal states and in the context of neuropsychiatric disorders. Here, we identify activating protein 2γ 3 (AP2γ 3, also known as Tcfap2c), originally described to regulate the generation of neurons in the developing cortex, as a modulator of adult hippocampal glutamatergic neurogenesis in mice. Specifically, AP2γ 3 is present in a sub-population of hippocampal transient amplifying progenitors. There, it is found to act as a positive regulator of the cell fate determinants Tbr2 and NeuroD, promoting proliferation and differentiation of new glutamatergic granular neurons. Conditional ablation of AP2γ 3 in the adult brain significantly reduced hippocampal neurogenesis and disrupted neural coherence between the ventral hippocampus and the medial prefrontal cortex. Furthermore, it resulted in the precipitation of multimodal cognitive deficits. This indicates that the sub-population of AP2γ 3-positive hippocampal progenitors may constitute an important cellular substrate for hippocampal-dependent cognitive functions. Concurrently, AP2γ 3 deletion produced significant impairments in contextual memory and reversal learning. More so, in a water maze reference memory task a delay in the transition to cognitive strategies relying on hippocampal function integrity was observed. Interestingly, anxiety- and d epressive-like behaviors were not significantly affected. Altogether, findings open new perspectives in understanding the role of specific sub-populations of newborn neurons in the (patho)physiology of neuropsychiatric disorders affecting hippocampal neuroplasticity and cognitive function in the adult brain.We acknowledge the excellent technical expertise of Luís Martins and Andrea Steiner-Mezzadri. We would also like to acknowledge Magdalena Götz for the insightful comments on the paper. AMP, PP, ARS, JS, VMS, NDA and JFO received fellowships from the Portuguese Foundation for Science and Technology (FCT). LP received fellowship from FCT and her work is funded by FCT (IF/01079/2014) and Bial Foundation (427/14) projects. This work was cofunded by the Life and Health Sciences Research Institute (ICVS), and Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (projects NORTE-01-0145- FEDER-000013 and NORTE-01-0145-FEDER-000023). This work has been also funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the FCT, under the scope of the project POCI-01-0145-FEDER-007038info:eu-repo/semantics/publishedVersionNature Publishing GroupUniversidade do MinhoPinheiro, António Maria Restolho MateusAlves, N. D.Patrício, Patrícia CarvalhoSantos, Ana Rita Machado dosCampos, E. LoureiroSilva, Joana Margarida Gonçalves MotaSardinha, Vanessa Alexandra MoraisReis, Joana Vanessa SantosSchorle, H.Oliveira, João Filipe Pedreira deNinkovic, J.Sousa, NunoPinto, Luísa Alexandra Meireles20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/49593eng1662-515310.1038/mp.2016.16927777416https://www.nature.cominfo: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:RCAAP2023-07-21T12:49:34Zoai:repositorium.sdum.uminho.pt:1822/49593Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:48:03.282050Repositório 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 |
AP2γ controls adult hippocampal neurogenesis and modulates cognitive, but not anxiety or depressive-like behavior |
title |
AP2γ controls adult hippocampal neurogenesis and modulates cognitive, but not anxiety or depressive-like behavior |
spellingShingle |
AP2γ controls adult hippocampal neurogenesis and modulates cognitive, but not anxiety or depressive-like behavior Pinheiro, António Maria Restolho Mateus Science & Technology |
title_short |
AP2γ controls adult hippocampal neurogenesis and modulates cognitive, but not anxiety or depressive-like behavior |
title_full |
AP2γ controls adult hippocampal neurogenesis and modulates cognitive, but not anxiety or depressive-like behavior |
title_fullStr |
AP2γ controls adult hippocampal neurogenesis and modulates cognitive, but not anxiety or depressive-like behavior |
title_full_unstemmed |
AP2γ controls adult hippocampal neurogenesis and modulates cognitive, but not anxiety or depressive-like behavior |
title_sort |
AP2γ controls adult hippocampal neurogenesis and modulates cognitive, but not anxiety or depressive-like behavior |
author |
Pinheiro, António Maria Restolho Mateus |
author_facet |
Pinheiro, António Maria Restolho Mateus Alves, N. D. Patrício, Patrícia Carvalho Santos, Ana Rita Machado dos Campos, E. Loureiro Silva, Joana Margarida Gonçalves Mota Sardinha, Vanessa Alexandra Morais Reis, Joana Vanessa Santos Schorle, H. Oliveira, João Filipe Pedreira de Ninkovic, J. Sousa, Nuno Pinto, Luísa Alexandra Meireles |
author_role |
author |
author2 |
Alves, N. D. Patrício, Patrícia Carvalho Santos, Ana Rita Machado dos Campos, E. Loureiro Silva, Joana Margarida Gonçalves Mota Sardinha, Vanessa Alexandra Morais Reis, Joana Vanessa Santos Schorle, H. Oliveira, João Filipe Pedreira de Ninkovic, J. Sousa, Nuno Pinto, Luísa Alexandra Meireles |
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 |
Pinheiro, António Maria Restolho Mateus Alves, N. D. Patrício, Patrícia Carvalho Santos, Ana Rita Machado dos Campos, E. Loureiro Silva, Joana Margarida Gonçalves Mota Sardinha, Vanessa Alexandra Morais Reis, Joana Vanessa Santos Schorle, H. Oliveira, João Filipe Pedreira de Ninkovic, J. Sousa, Nuno Pinto, Luísa Alexandra Meireles |
dc.subject.por.fl_str_mv |
Science & Technology |
topic |
Science & Technology |
description |
Hippocampal neurogenesis has been proposed to participate in a myriad of behavioral responses, both in basal states and in the context of neuropsychiatric disorders. Here, we identify activating protein 2γ 3 (AP2γ 3, also known as Tcfap2c), originally described to regulate the generation of neurons in the developing cortex, as a modulator of adult hippocampal glutamatergic neurogenesis in mice. Specifically, AP2γ 3 is present in a sub-population of hippocampal transient amplifying progenitors. There, it is found to act as a positive regulator of the cell fate determinants Tbr2 and NeuroD, promoting proliferation and differentiation of new glutamatergic granular neurons. Conditional ablation of AP2γ 3 in the adult brain significantly reduced hippocampal neurogenesis and disrupted neural coherence between the ventral hippocampus and the medial prefrontal cortex. Furthermore, it resulted in the precipitation of multimodal cognitive deficits. This indicates that the sub-population of AP2γ 3-positive hippocampal progenitors may constitute an important cellular substrate for hippocampal-dependent cognitive functions. Concurrently, AP2γ 3 deletion produced significant impairments in contextual memory and reversal learning. More so, in a water maze reference memory task a delay in the transition to cognitive strategies relying on hippocampal function integrity was observed. Interestingly, anxiety- and d epressive-like behaviors were not significantly affected. Altogether, findings open new perspectives in understanding the role of specific sub-populations of newborn neurons in the (patho)physiology of neuropsychiatric disorders affecting hippocampal neuroplasticity and cognitive function in the adult brain. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017 2017-01-01T00:00:00Z |
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/1822/49593 |
url |
https://hdl.handle.net/1822/49593 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1662-5153 10.1038/mp.2016.169 27777416 https://www.nature.com |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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