Constitutive deficiency of the neurogenic hippocampal modulator AP2γ promotes anxiety-like behavior and cumulative memory deficits in mice from juvenile to adult periods
- University of Minho, Portugal
- Columbia University Medical Center, United States
Abstract
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file;Source Data file has been provided for Figure 1.Source Code files have been provided for Figure 6 and for Figure 6 - Figure supplement 1.
Article and author information
Author details
Tiago Silveira-Rosa
Ana João Rodrigues
Funding
Fundação para a Ciência e a Tecnologia (SFRH/BD/131278/2017)
- Eduardo Loureiro-Campos
Fundação para a Ciência e a Tecnologia (UIDB/50026/2020 and UIDP/50026/2020)
- Eduardo Loureiro-Campos
- António Mateus-Pinheiro
- Joana Silva
- Vanessa Morais Sardinha
- Bárbara Mendes-Pinheiro
- Tiago Silveira-Rosa
- Ana Verónica Domingues
- Ana João Rodrigues
- João Oliveira
- Nuno Sousa
- Luísa Pinto
Fundação para a Ciência e a Tecnologia (PPBI-POCI-01-0145-FEDER-022122)
- Eduardo Loureiro-Campos
- António Mateus-Pinheiro
- Joana Silva
- Vanessa Morais Sardinha
- Bárbara Mendes-Pinheiro
- Tiago Silveira-Rosa
- Ana Verónica Domingues
- Ana João Rodrigues
- João Oliveira
- Nuno Sousa
- Luísa Pinto
Fundação para a Ciência e a Tecnologia (SRFH/BD/120124/2016)
- Bárbara Mendes-Pinheiro
Fundação para a Ciência e a Tecnologia (SFRH/BD/135273/2017)
- Tiago Silveira-Rosa
Fundação para a Ciência e a Tecnologia (SFRH/BD/147066/2019)
- Ana Verónica Domingues
Fundação para a Ciência e a Tecnologia (CEECIND/03887/2017)
- Carina Soares-Cunha
Fundação para a Ciência e a Tecnologia (IF/00328/2015,IF/01079/2014; PTDC/MED-NEU/31417/2017)
- João Oliveira
Fundação para a Ciência e a Tecnologia (2020.02855.CEECIND)
- Luísa Pinto
Fundação Bial (037/18)
- João Oliveira
Fundação Bial (427/14)
- Luísa Pinto
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- D Nora Abrous, Neurocentre Magendie, INSERM, France
Ethics
Animal experimentation: Efforts were made to minimize the number of animals and their suffering. All experimental procedures performed in this work were conducted in accordance with the EU Directive 2010/63/EU and approved by the Portuguese National Authority for animal experimentation, Direção-Geral de Alimentação e Veterinária (DGAV) with the project reference 0420/000/000/2011 (DGAV 4542).
Version history
- Received: May 26, 2021
- Preprint posted: June 8, 2021 (view preprint)
- Accepted: December 2, 2021
- Accepted Manuscript published: December 3, 2021 (version 1)
- Version of Record published: December 24, 2021 (version 2)
Copyright
© 2021, Loureiro-Campos et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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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
eLife 10:e70685.
https://doi.org/10.7554/eLife.70685
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