Department of Clinical Neurobiology at the German Cancer Research Center (DKFZ) and the Medical Faculty of the Heidelberg University, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Department of Clinical Neurobiology at the German Cancer Research Center (DKFZ) and the Medical Faculty of the Heidelberg University, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Neuron. 2017 Apr 5;94(1):125-137.e5. doi: 10.1016/j.neuron.2017.03.003. Epub 2017 Mar 23.
Plasticity of adult neurogenesis supports adaptation to environmental changes. The identification of molecular mediators that signal these changes to neural progenitors in the niche has remained elusive. Here we report that diazepam binding inhibitor (DBI) is crucial in supporting an adaptive mechanism in response to changes in the environment. We provide evidence that DBI is expressed in stem cells in all neurogenic niches of the postnatal brain. Focusing on the hippocampal subgranular zone (SGZ) and employing multiple genetic manipulations in vivo, we demonstrate that DBI regulates the balance between preserving the stem cell pool and neurogenesis. Specifically, DBI dampens GABA activity in stem cells, thereby sustaining the proproliferative effect of physical exercise and enriched environment. Our data lend credence to the notion that the modulatory effect of DBI constitutes a general mechanism that regulates postnatal neurogenesis.
成人神经发生的可塑性支持对环境变化的适应。然而，识别向龛内神经祖细胞发出这些变化信号的分子介质仍然难以捉摸。在这里，我们报告说，地西泮结合抑制剂（DBI）对于支持对环境变化的适应机制至关重要。我们提供的证据表明，DBI 在后脑所有神经发生龛位的干细胞中表达。我们专注于海马亚颗粒区（SGZ），并在体内进行多种遗传操作，证明 DBI 调节干细胞池和神经发生之间的平衡。具体而言，DBI 抑制干细胞中的 GABA 活性，从而维持体育锻炼和丰富环境的促增殖作用。我们的数据证明了 DBI 的调节作用构成了调节产后神经发生的一般机制的观点。
