Nonsynaptic GABA signaling in postnatal subventricular zone controls proliferation of GFAP-expressing progenitors
Nonsynaptic GABA signaling in postnatal subventricular zone controls proliferation of GFAP-expressing progenitors
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DOI：
10.1038/nn1522
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发表时间：
2005-09-01
影响因子：
25
通讯作者：
Bordey, A
中科院分区：
文献类型：
--
作者：
Liu, XX;Wang, Q;Bordey, A
在出生后心室下区（SVZ），神经母细胞释放的局部信号或信号分子限制了被认为是干细胞的表达胶质纤维酸性蛋白（GFAP）的祖细胞的增殖。然而，SVZ细胞之间的信号尚未被识别。我们发现，神经母细胞的去极化在表达gap的细胞中诱导非突触snare -独立的GABA(A)受体电流，其时间过程取决于急性小鼠切片中GABA的摄取。我们发现，GABA(A)受体在表达gmap的细胞中被强直激活，这与神经母细胞中自发去极化的存在一致，这足以诱导GABA释放。这些数据表明，神经母细胞和表达gmap的细胞之间存在非突触性gaba能信号。此外，我们发现表达gap的细胞中GABA(A)受体的激活限制了它们在细胞周期中的进展。因此，当表达gfap的细胞生成成神经细胞时，成神经细胞释放的GABA通过激活GABA(a)受体提供了一种反馈机制来控制表达gfap的祖细胞的增殖。
In the postnatal subventricular zone ( SVZ), local cues or signaling molecules released from neuroblasts limit the proliferation of glial fibrillary acidic protein (GFAP)-expressing progenitors thought to be stem cells. However, signals between SVZ cells have not been identified. We show that depolarization of neuroblasts induces nonsynaptic SNARE-independent GABA(A) receptor currents in GFAP-expressing cells, the time course of which depends on GABA uptake in acute mouse slices. We found that GABA(A) receptors are tonically activated in GFAP-expressing cells, consistent with the presence of spontaneous depolarizations in neuroblasts that are sufficient to induce GABA release. These data demonstrate the existence of nonsynaptic GABAergic signaling between neuroblasts and GFAP-expressing cells. Furthermore, we show that GABA(A) receptor activation in GFAP-expressing cells limits their progression through the cell cycle. Thus, as GFAP-expressing cells generate neuroblasts, GABA released from neuroblasts provides a feedback mechanism to control the proliferation of GFAP-expressing progenitors by activating GABA(A) receptors.