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成年小鼠海马区神经祖细胞对外切ATP酶NTPDase2和核苷酸受体的功能性表达。

Functional expression of the ecto-ATPase NTPDase2 and of nucleotide receptors by neuronal progenitor cells in the adult murine hippocampus.

作者信息

Shukla Varsha, Zimmermann Herbert, Wang Liping, Kettenmann Helmut, Raab Sabine, Hammer Klaus, Sévigny Jean, Robson Simon C, Braun Norbert

机构信息

Biocenter, J.W. Goethe-University, AK Neurochemistry, Frankfurt am Main, Germany.

出版信息

J Neurosci Res. 2005 Jun 1;80(5):600-10. doi: 10.1002/jnr.20508.

Abstract

An astrocyte-like cell population corresponding to residual radial glia represents the neuronal progenitors of the adult mammalian hippocampus. We show that radial glia-like cells of the dentate gyrus express surface-located ATP-hydrolyzing activity and are immunopositive for NTPDase2. This enzyme hydrolyzes extracellular nucleoside triphosphates such as ATP and UTP to their nucleoside diphosphates and is thus involved in the control of signaling via P2 receptors. NTPDase2 is expressed from embryonic day 17 onward. In the hippocampus, the embryonic pattern of NTPDase2 expression mirrors that of the dentate migration of neuroblasts. Double-immunolabeling revealed that NTPDase2 is associated with subpopulations of glial fibrillary acidic protein-, nestin- and doublecortin-positive radial cells. It is absent from mature granule cells or S100-positive astrocytes. NTPDase2-positive cells proliferate. Furthermore, after mitosis, progenitor cells preferentially reveal an NTPDase2-positive phenotype. Patch-clamp analysis demonstrates functional nucleotide receptors in progenitor cells expressing nestin promotor-driven green fluorescent protein. Our results identify the ecto-nucleotidase NTPDase2 and functional P2X receptors at hippocampal progenitor cells. We infer that signaling pathways via extracellular nucleotides may play a role in the control of hippocampal neurogenesis.

摘要

对应于残留放射状胶质细胞的星形胶质样细胞群体代表成年哺乳动物海马体的神经元祖细胞。我们发现齿状回的放射状胶质样细胞表达位于表面的ATP水解活性,并且对NTPDase2呈免疫阳性。这种酶将细胞外三磷酸核苷如ATP和UTP水解为其二磷酸核苷,因此参与通过P2受体的信号传导控制。NTPDase2从胚胎第17天开始表达。在海马体中,NTPDase2表达的胚胎模式反映了神经母细胞的齿状迁移模式。双重免疫标记显示NTPDase2与胶质纤维酸性蛋白、巢蛋白和双皮质素阳性放射状细胞的亚群相关。成熟颗粒细胞或S100阳性星形胶质细胞中不存在NTPDase2。NTPDase2阳性细胞增殖。此外,有丝分裂后,祖细胞优先呈现NTPDase2阳性表型。膜片钳分析证明在表达巢蛋白启动子驱动的绿色荧光蛋白的祖细胞中有功能性核苷酸受体。我们的结果确定了海马体祖细胞中的胞外核苷酸酶NTPDase2和功能性P2X受体。我们推断通过细胞外核苷酸的信号通路可能在海马体神经发生的控制中起作用。

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