Constitutive AP2gamma deficiency reduces postnatal hippocampal neurogenesis and induces behavioral deficits in juvenile mice that persist during adulthood

Loureiro-Campos, E.; Alves, N. D.; Mateus-Pinheiro, A.; Patricio, P.; Soares-Cunha, C.; Silva, J.; Sardinha, V. M.; Mendes-Pinheiro, B.; Silveira-Rosa, T.; Rodrigues, A. J.; Oliveira, J.; Sousa, N.; Pinto, L.

doi:10.1101/2021.06.07.447328

bioRxiv · 10.1101/2021.06.07.447328

Constitutive AP2gamma deficiency reduces postnatal hippocampal neurogenesis and induces behavioral deficits in juvenile mice that persist during adulthood

Loureiro-Campos, E.·Alves, N. D.·Mateus-Pinheiro, A.·Patricio, P.·Soares-Cunha, C.·Silva, J.·Sardinha, V. M.·Mendes-Pinheiro, B.·Silveira-Rosa, T.·Rodrigues, A. J.·Oliveira, J.·Sousa, N.·Pinto, L.

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Abstract

The transcription factor activating protein two gamma (AP2{gamma}) 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 AP2{gamma} heterozygous deletion in mice from early postnatal development until adulthood. Constitutive AP2{gamma} 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, AP2{gamma} deficiency impairs dorsal hippocampus-to-prefrontal cortex functional connectivity. We observed a progressive and cumulative impact of constitutive AP2{gamma} 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 AP2{gamma} in the generation of glutamatergic neurons in the postnatal brain and its impact on behavioral performance.

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Loureiro-Campos, E., Alves, N. D., Mateus-Pinheiro, A., Patricio, P., Soares-Cunha, C., Silva, J., Sardinha, V. M., Mendes-Pinheiro, B., Silveira-Rosa, T., Rodrigues, A. J., Oliveira, J., Sousa, N., Pinto, L.. 2021-06-08. Constitutive AP2gamma deficiency reduces postnatal hippocampal neurogenesis and induces behavioral deficits in juvenile mice that persist during adulthood. https://doi.org/10.1101/2021.06.07.447328

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