RT Journal Article
SR Electronic
T1 Constitutive AP2γ deficiency reduces postnatal hippocampal neurogenesis and induces behavioral deficits in juvenile mice that persist during adulthood
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.07.447328
DO 10.1101/2021.06.07.447328
A1 Eduardo Loureiro-Campos
A1 Nuno Dinis Alves
A1 António Mateus-Pinheiro
A1 Patrícia Patrício
A1 Carina Soares-Cunha
A1 Joana Silva
A1 Vanessa Morais Sardinha
A1 Bárbara Mendes-Pinheiro
A1 Tiago Silveira-Rosa
A1 Ana João Rodrigues
A1 João Filipe Oliveira
A1 Nuno Sousa
A1 Luísa Pinto
YR 2021
UL http://biorxiv.org/content/early/2021/06/08/2021.06.07.447328.abstract
AB 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 AP2γ heterozygous deletion in mice from early postnatal development until adulthood. Constitutive AP2γ heterozygous deletion in mice caused a reduction of hippocampal transient amplifying progenitors (TAPs) in the postnatal brain, inducing significant impairments on hippocampal-dependent emotional- and cognitive-behavioral tasks including anxiety-like behavior and cognitive deficits, typically associated with an intact neurogenic activity. Moreover, AP2γ deficiency impairs dorsal hippocampus-to-prefrontal cortex functional connectivity.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 impairments on emotional and cognitive behaviors from juvenile to adult periods. Collectively, the results herein presented demonstrate the importance of AP2γ in the generation of glutamatergic neurons in the postnatal brain and its impact on behavioral performance.Competing Interest StatementThe authors have declared no competing interest.