Embryology and Stem Cell Biology, Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058 Basel, Switzerland.
Development. 2014 Jan;141(1):83-90. doi: 10.1242/dev.102608. Epub 2013 Nov 27.
Adult neurogenesis is tightly regulated through the interaction of neural stem/progenitor cells (NSCs) with their niche. Neurotransmitters, including GABA activation of GABAA receptor ion channels, are important niche signals. We show that adult mouse hippocampal NSCs and their progeny express metabotropic GABAB receptors. Pharmacological inhibition of GABAB receptors stimulated NSC proliferation and genetic deletion of GABAB1 receptor subunits increased NSC proliferation and differentiation of neuroblasts in vivo. Cell-specific conditional deletion of GABAB receptors supports a cell-autonomous role in newly generated cells. Our data indicate that signaling through GABAB receptors is an inhibitor of adult neurogenesis.
成人神经发生是通过神经干细胞/祖细胞(NSCs)与其龛之间的相互作用来严格调控的。神经递质,包括 GABA 激活 GABAA 受体离子通道,是重要的龛信号。我们表明成年小鼠海马 NSCs 及其后代表达代谢型 GABAB 受体。GABAB 受体的药理学抑制刺激 NSC 增殖,GABAB1 受体亚单位的基因缺失增加体内神经母细胞的 NSC 增殖和分化。细胞特异性条件性 GABAB 受体缺失支持新生成细胞中的细胞自主作用。我们的数据表明,GABAB 受体信号是成人神经发生的抑制剂。