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

eLife

Ana João Rodrigues¹  António Mateus-Pinheiro²  Vanessa Morais Sardinha²  Nuno Sousa²  Ana Verónica Domingues²  Carina Soares-Cunha²  Bárbara Mendes-Pinheiro²  Eduardo Loureiro-Campos²  Luísa Pinto²  Patrícia Patrício²  Nuno Dinis Alves²  Tiago Silveira-Rosa²  Joana Silva²  João Oliveira³ 

[1] Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal;Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal;ICVS/3B’s -PT Government Associate Laboratory, Guimarães, Portugal;Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal;ICVS/3B’s -PT Government Associate Laboratory, Guimarães, Portugal;IPCA-EST-2Ai, Polytechnic Institute of Cávado and Ave, Applied Artificial Intelligence Laboratory, Campus of IPCA, Barcelos, Portugal;

关键词: hippocampal neurogenesis;    ap2gamma;    development;    anxiety;    cognition;    spectral coherence;    Mouse;   

DOI  :  10.7554/eLife.70685

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY