Neurons control the expression of connexin 30 and connexin 43 in mouse cortical astrocytes
Neurons control the expression of connexin 30 and connexin 43 in mouse cortical astrocytes
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DOI：
10.1002/glia.20698
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发表时间：
2008-09-01
期刊：
影响因子：
6.2
通讯作者：
Giaume, Christian
中科院分区：
文献类型：
--
作者：
Koulakoff, Annette;Ezan, Pascal;Giaume, Christian
星形胶质细胞的一个特征是其由间隙连接介导的高水平细胞间通讯。在成人大脑星形胶质细胞中形成这些连接的两种主要连接蛋白 Cx30 和 Cx43 显示出不同的发育和区域表达，其中 Cx30 的出现延迟。在新生儿大脑皮层星形胶质细胞的原代培养物中，虽然 Cx43 大量表达，但未检测到 Cx30。在本报告中，在星形胶质细胞/神经元共培养物中进行的蛋白质印迹和共聚焦免疫荧光分析表明，神经元上调 Cx43 的表达，并诱导优先位于神经元胞体附近的星形胶质细胞亚群中的 Cx30 表达。在与神经元共培养的缺乏星形胶质细胞的 Cx43 中，Cx30 的诱导允许恢复 Cx30 阳性星形胶质细胞胰岛内的染料偶联，表明由 Cx30 形成的细胞间通道具有功能。神经元对皮质星形胶质细胞连接蛋白表达的上调作用与其电活动无关，并且需要两种细胞类型之间的紧密相互作用。在神经毒性治疗引起的神经元死亡后，这种效应会逆转。此外，触发体内神经元死亡的兴奋性毒性治疗导致位于神经元耗尽区域内的反应性星形胶质细胞中的两种连接蛋白下调。总而言之，这些观察结果表明两种主要星形胶质细胞连接蛋白的表达受到神经元的严格调节。 (C) 2008 Wiley-Liss, Inc.
A characteristic feature of astrocytes is their high level of intercellular communication mediated by gap junctions. The two main connexins, Cx30 and Cx43, that form these junctions in astrocytes of adult brain display different developmental and regional expression, with a delayed onset of appearance for Cx30. In primary cultures of astrocytes from newborn cerebral cortex, while Cx43 is abundantly expressed, Cx30 is not detectable. In the present report, Western blot and confocal immunofluorescence analysis performed in astrocyte/neuron cocultures demonstrate that neurons upregulate the expression of Cx43 and induce that of Cx30 in subsets of astrocytes preferentially located in close proximity to neuronal soma. In Cx43 lacking astrocytes cocultured with neurons, the induction of Cx30 allows the restoration of dye coupling within islets of Cx30-positive astrocytes, indicating that intercellular channels formed by Cx30 are functional. The upregulating effect of neurons on the expression of connexins in cortical astrocytes is independent of their electrical activity and requires tight interactions between both cell types. This effect is reversed after neuronal death induced by neurotoxic treatments. Furthermore, excitotoxic treatments triggering neuronal death in vivo lead to a downregulation of both connexins in reactive astrocytes located within the area depleted in neurons. Altogether these observations indicate that the expression of the two main astrocyte connexins is tightly regulated by neurons. (C) 2008 Wiley-Liss, Inc.