Activation of the GABA(A) receptor inhibits the proliferative effects of bFGF in cortical progenitor cells
Activation of the GABA(A) receptor inhibits the proliferative effects of bFGF in cortical progenitor cells
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DOI：
10.1111/j.1460-9568.1997.tb01399.x
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发表时间：
1997-02-01
影响因子：
3.4
通讯作者：
Parnavelas, JG
中科院分区：
文献类型：
--
作者：
Antonopoulos, J;Pappas, IS;Parnavelas, JG
最近的研究定位了含有γ-氨基丁酸（GABA）的神经元，并鉴定了在发育中的大脑皮层的增殖区表达GABA（A）受体亚基的细胞，并证明了GABA在皮质神经发生中的作用。我们在此研究了许多已知参与皮质细胞增殖和分化的神经营养因子与 GABA 能系统（GABA 和 GABA(A) 受体）在离解皮质细胞培养物中细胞生产调节中的相互作用。我们发现碱性成纤维细胞生长因子 (bFGF) 增加了标记 GABA(A) 受体 α(1) 亚基的细胞数量，但不增加标记 α(2)、α(3) 或 α(5) 亚基的细胞数量。大多数增殖的神经上皮细胞以及分化的神经元表达α(1)亚基。我们还发现，GABA 或蝇蕈醇激活 GABAA 受体会抑制 bFGF 对皮质祖细胞的增殖作用，导致分化神经元数量增加。这些结果表明，bFGF 刺激发育中新皮质的培养祖细胞中的细胞增殖和 GABAA 受体表达，并且 GABA 通过提供终止细胞分裂的反馈信号来调节细胞生成。
Recent studies have localized gamma-aminobutyric acid (GABA)-containing neurons and identified cells that express subunits of the GABA(A) receptor in the proliferative zone of the developing cerebral cortex and have demonstrated a role for GABA in cortical neurogenesis. We examined here the interactions between a number of neurotrophic factors, known to be involved in cortical cell proliferation and differentiation, and the GABAergic system (GABA and GABA(A) receptors) in the regulation of cell production in dissociated cortical cell cultures. We found that basic fibroblast growth factor (bFGF) increased the number of cells labelled for the alpha(1) subunit of the GABA(A) receptor but not for the alpha(2), alpha(3) or alpha(5) subunits. The alpha(1) subunit was expressed by the majority of proliferating neuroepithelial cells as well as by differentiated neurons. We also found that activation of the GABAA receptor by GABA or muscimol inhibited the proliferative effects of bFGF on cortical progenitors, leading to an increased number of differentiated neurons, These results suggest that bFGF stimulates cell proliferation and GABAA receptor expression in cultured progenitor cells of the developing neocortex, and that GABA regulates cell production by providing a feedback signal that terminates cell division.