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Constitutive deficiency of the neurogenic hippocampal modulator AP2γ promotes anxiety-like behavior and cumulative memory deficits in mice from juvenile to adult periods

The transcription factor activating protein two gamma (AP2γ) is an important regulator of neurogenesis both during embryonic development as well as in the postnatal brain, but its role for neurophysiology and behavior at distinct postnatal periods is still unclear. In this work, we explored the neur...

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Autores principales: Loureiro-Campos, Eduardo, Mateus-Pinheiro, António, Patrício, Patrícia, Soares-Cunha, Carina, Silva, Joana, Sardinha, Vanessa Morais, Mendes-Pinheiro, Bárbara, Silveira-Rosa, Tiago, Domingues, Ana Verónica, Rodrigues, Ana João, Oliveira, João, Sousa, Nuno, Alves, Nuno Dinis, Pinto, Luísa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709574/
https://www.ncbi.nlm.nih.gov/pubmed/34859784
http://dx.doi.org/10.7554/eLife.70685
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author Loureiro-Campos, Eduardo
Mateus-Pinheiro, António
Patrício, Patrícia
Soares-Cunha, Carina
Silva, Joana
Sardinha, Vanessa Morais
Mendes-Pinheiro, Bárbara
Silveira-Rosa, Tiago
Domingues, Ana Verónica
Rodrigues, Ana João
Oliveira, João
Sousa, Nuno
Alves, Nuno Dinis
Pinto, Luísa
author_facet Loureiro-Campos, Eduardo
Mateus-Pinheiro, António
Patrício, Patrícia
Soares-Cunha, Carina
Silva, Joana
Sardinha, Vanessa Morais
Mendes-Pinheiro, Bárbara
Silveira-Rosa, Tiago
Domingues, Ana Verónica
Rodrigues, Ana João
Oliveira, João
Sousa, Nuno
Alves, Nuno Dinis
Pinto, Luísa
author_sort Loureiro-Campos, Eduardo
collection PubMed
description The transcription factor activating protein two gamma (AP2γ) is an important regulator of neurogenesis both during embryonic development as well as in the postnatal brain, but its role for neurophysiology and behavior at distinct postnatal periods is still unclear. In this work, we explored the neurogenic, behavioral, and functional impact of a constitutive and heterozygous AP2γ deletion in mice from early postnatal development until adulthood. AP2γ deficiency promotes downregulation of hippocampal glutamatergic neurogenesis, altering the ontogeny of emotional and memory behaviors associated with hippocampus formation. The impairments induced by AP2γ constitutive deletion since early development leads to an anxious-like phenotype and memory impairments as early as the juvenile phase. These behavioral impairments either persist from the juvenile phase to adulthood or emerge in adult mice with deficits in behavioral flexibility and object location recognition. Collectively, we observed a progressive and cumulative impact of constitutive AP2γ deficiency on the hippocampal glutamatergic neurogenic process, as well as alterations on limbic-cortical connectivity, together with functional behavioral impairments. The results herein presented demonstrate the modulatory role exerted by the AP2γ transcription factor and the relevance of hippocampal neurogenesis in the development of emotional states and memory processes.
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spelling pubmed-87095742022-01-04 Constitutive deficiency of the neurogenic hippocampal modulator AP2γ promotes anxiety-like behavior and cumulative memory deficits in mice from juvenile to adult periods Loureiro-Campos, Eduardo Mateus-Pinheiro, António Patrício, Patrícia Soares-Cunha, Carina Silva, Joana Sardinha, Vanessa Morais Mendes-Pinheiro, Bárbara Silveira-Rosa, Tiago Domingues, Ana Verónica Rodrigues, Ana João Oliveira, João Sousa, Nuno Alves, Nuno Dinis Pinto, Luísa eLife Developmental Biology The transcription factor activating protein two gamma (AP2γ) is an important regulator of neurogenesis both during embryonic development as well as in the postnatal brain, but its role for neurophysiology and behavior at distinct postnatal periods is still unclear. In this work, we explored the neurogenic, behavioral, and functional impact of a constitutive and heterozygous AP2γ deletion in mice from early postnatal development until adulthood. AP2γ deficiency promotes downregulation of hippocampal glutamatergic neurogenesis, altering the ontogeny of emotional and memory behaviors associated with hippocampus formation. The impairments induced by AP2γ constitutive deletion since early development leads to an anxious-like phenotype and memory impairments as early as the juvenile phase. These behavioral impairments either persist from the juvenile phase to adulthood or emerge in adult mice with deficits in behavioral flexibility and object location recognition. Collectively, we observed a progressive and cumulative impact of constitutive AP2γ deficiency on the hippocampal glutamatergic neurogenic process, as well as alterations on limbic-cortical connectivity, together with functional behavioral impairments. The results herein presented demonstrate the modulatory role exerted by the AP2γ transcription factor and the relevance of hippocampal neurogenesis in the development of emotional states and memory processes. eLife Sciences Publications, Ltd 2021-12-03 /pmc/articles/PMC8709574/ /pubmed/34859784 http://dx.doi.org/10.7554/eLife.70685 Text en © 2021, Loureiro-Campos et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology
Loureiro-Campos, Eduardo
Mateus-Pinheiro, António
Patrício, Patrícia
Soares-Cunha, Carina
Silva, Joana
Sardinha, Vanessa Morais
Mendes-Pinheiro, Bárbara
Silveira-Rosa, Tiago
Domingues, Ana Verónica
Rodrigues, Ana João
Oliveira, João
Sousa, Nuno
Alves, Nuno Dinis
Pinto, Luísa
Constitutive deficiency of the neurogenic hippocampal modulator AP2γ promotes anxiety-like behavior and cumulative memory deficits in mice from juvenile to adult periods
title Constitutive deficiency of the neurogenic hippocampal modulator AP2γ promotes anxiety-like behavior and cumulative memory deficits in mice from juvenile to adult periods
title_full Constitutive deficiency of the neurogenic hippocampal modulator AP2γ promotes anxiety-like behavior and cumulative memory deficits in mice from juvenile to adult periods
title_fullStr Constitutive deficiency of the neurogenic hippocampal modulator AP2γ promotes anxiety-like behavior and cumulative memory deficits in mice from juvenile to adult periods
title_full_unstemmed Constitutive deficiency of the neurogenic hippocampal modulator AP2γ promotes anxiety-like behavior and cumulative memory deficits in mice from juvenile to adult periods
title_short Constitutive deficiency of the neurogenic hippocampal modulator AP2γ promotes anxiety-like behavior and cumulative memory deficits in mice from juvenile to adult periods
title_sort constitutive deficiency of the neurogenic hippocampal modulator ap2γ promotes anxiety-like behavior and cumulative memory deficits in mice from juvenile to adult periods
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709574/
https://www.ncbi.nlm.nih.gov/pubmed/34859784
http://dx.doi.org/10.7554/eLife.70685
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