Mateus-Pinheiro Antonio, Alves Nuno Dinis, Sousa Nuno, Pinto Luisa
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
J Exp Neurosci. 2018 Apr 2;12:1179069518766897. doi: 10.1177/1179069518766897. eCollection 2018.
Since the recognition that the mammalian brain retains the ability to generate newborn neurons with functional relevance throughout life, the matrix of molecular regulators that govern adult neurogenesis has been the focus of much interest. In a recent study published in , we demonstrate Activating Protein 2γ (AP2γ), a transcription factor previously implicated in cell fate determination in the developing cortex, as a novel player in the regulation of glutamatergic neurogenesis in the adult hippocampus. Using distinct experimental approaches, we showed that AP2γ is specifically present in a subpopulation of transient amplifying progenitors, where it acts as a crucial promoter of proliferation and differentiation of adult-born glutamatergic granule neurons. Strikingly, deficiency of AP2γ in the adult brain compromises the generation of new glutamatergic neurons, with impact on the function of cortico-limbic circuits. Here, we share our view on how AP2γ integrates the transcriptional orchestration of glutamatergic neurogenesis in the adult hippocampus, and consequently, how it emerges as a novel molecular candidate to study the translation of environmental pressures into alterations of brain neuroplasticity in homeostatic, but also in neuropathological contexts.
自从认识到哺乳动物大脑在整个生命过程中都保留着产生具有功能相关性的新生神经元的能力以来，控制成体神经发生的分子调节因子矩阵一直是人们非常感兴趣的焦点。在最近发表于《》的一项研究中，我们证明了激活蛋白2γ（AP2γ），一种先前与发育中的皮质细胞命运决定有关的转录因子，是成年海马体中谷氨酸能神经发生调节的新参与者。通过不同的实验方法，我们表明AP2γ特异性存在于瞬时扩增祖细胞的一个亚群中，在那里它作为成年产生的谷氨酸能颗粒神经元增殖和分化的关键促进因子发挥作用。令人惊讶的是，成年大脑中AP2γ的缺乏会损害新的谷氨酸能神经元的产生，从而影响皮质-边缘回路的功能。在这里，我们分享我们对于AP2γ如何整合成年海马体中谷氨酸能神经发生的转录调控的观点，以及因此它如何成为一个新的分子候选物，用于研究在稳态以及神经病理学背景下环境压力如何转化为大脑神经可塑性改变的问题。
