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

神经源性海马调节剂 AP2γ 的组成性缺陷导致小鼠从幼年到成年时期出现焦虑样行为和累积记忆缺陷

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作者:Eduardo Loureiro-Campos, António Mateus-Pinheiro, Patrícia Patrício, Carina Soares-Cunha, Joana Silva, Vanessa Morais Sardinha, Bárbara Mendes-Pinheiro, Tiago Silveira-Rosa, Ana Verónica Domingues, Ana João Rodrigues, João Oliveira, Nuno Sousa, Nuno Dinis Alves #, Luísa Pinto #

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.

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