Everlien Isabelle, Yen Ting-Yun, Liu Yu-Chao, Di Marco Barbara, Vázquez-Marín Javier, Centanin Lázaro, Alfonso Julieta, Monyer Hannah
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; Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan.
Neuron. 2022 Oct 5;110(19):3139-3153.e6. doi: 10.1016/j.neuron.2022.07.022. Epub 2022 Aug 22.
Of the neurotransmitters that influence neurogenesis, gamma-aminobutyric acid (GABA) plays an outstanding role, and GABA receptors support non-synaptic signaling in progenitors and migrating neurons. Here, we report that expression levels of diazepam binding inhibitor (DBI), an endozepine that modulates GABA signaling, regulate embryonic neurogenesis, affecting the long-term outcome regarding the number of neurons in the postnatal mouse brain. We demonstrate that DBI is highly expressed in radial glia and intermediate progenitor cells in the germinal zones of the embryonic mouse brain that give rise to excitatory and inhibitory cells. The mechanism by which DBI controls neurogenesis involves its action as a negative allosteric modulator of GABA-induced currents on progenitor cells that express GABA receptors containing γ subunits. DBI's modulatory effect parallels that of GABA-receptor-mediating signaling in these cells in the proliferative areas, reflecting the tight control that DBI exerts on embryonic neurogenesis.
在影响神经发生的神经递质中，γ-氨基丁酸（GABA）起着突出作用，且GABA受体支持祖细胞和迁移神经元中的非突触信号传导。在此，我们报告，地西泮结合抑制剂（DBI）作为一种调节GABA信号传导的内源性苯二氮䓬，其表达水平可调节胚胎神经发生，影响出生后小鼠脑中神经元数量的长期结果。我们证明，DBI在胚胎小鼠脑生发区的放射状胶质细胞和中间祖细胞中高度表达，这些细胞可产生兴奋性和抑制性细胞。DBI控制神经发生的机制涉及其作为GABA诱导电流的负变构调节剂对表达含γ亚基的GABA受体的祖细胞的作用。在增殖区域，DBI的调节作用与这些细胞中GABA受体介导的信号传导作用相似，这反映了DBI对胚胎神经发生的严格控制。
