Deletion of astroglial connexins weakens the blood-brain barrier
Deletion of astroglial connexins weakens the blood-brain barrier
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DOI：
10.1038/jcbfm.2012.45
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发表时间：
2012-08-01
影响因子：
6.3
通讯作者：
Cohen-Salmon, Martine
中科院分区：
文献类型：
--
作者：
Ezan, Pascal;Andre, Pascal;Cohen-Salmon, Martine
星形胶质细胞是大脑中最突出的胶质细胞类型，其发出称为终足的专门过程，其包裹血管并表达专用于血管系统生理学的大分子库。星形胶质细胞尾足最显著的特性之一是它们富含间隙连接蛋白连接蛋白43和30（Cx43和Cx 30），从而允许离子和小信号分子通过血管周围星形胶质细胞网络的直接细胞间运输。星形胶质细胞连接蛋白对脑血管系统生理学的贡献从未被提及。在这里，我们表明，Cx43和Cx 30的表达在血管周围的endfeet水平从出生后第2和12天开始，并在出生后第15和20天分别完全成熟，表明星形胶质细胞血管周围的连接发生和发展在出生后血脑屏障（BBB）成熟。我们证明，小鼠缺乏Cx 30和Cx43的GFAP（胶质细胞酸性蛋白）阳性细胞显示星形胶质细胞端足水肿和部分损失的星形胶质细胞水通道水通道蛋白-4和β-肌营养不良蛋白聚糖，跨膜受体锚定星形胶质细胞端足血管周围的基底层。此外，星形胶质细胞连接蛋白的缺乏削弱了血脑屏障，血脑屏障在血管静压和剪切应力增加时开放。这些结果表明，星形胶质细胞连接蛋白是必要的，以维持BBB的完整性。Journal of Cerebral Blood Flow & Metabolism（2012）32，1457-1467; doi：10.1038/jcbfm.2012.45; 2012年4月4日在线发表
Astrocytes, the most prominent glial cell type in the brain, send specialized processes named endfeet, which enwrap blood vessels and express a large molecular repertoire dedicated to the physiology of the vascular system. One of the most striking properties of astrocyte endfeet is their enrichment in gap junction protein connexins 43 and 30 (Cx43 and Cx30) allowing for direct intercellular trafficking of ions and small signaling molecules through perivascular astroglial networks. The contribution of astroglial connexins to the physiology of the brain vascular system has never been addressed. Here, we show that Cx43 and Cx30 expression at the level of perivascular endfeet starts from postnatal days 2 and 12 and is fully mature at postnatal days 15 and 20, respectively, indicating that astroglial perivascular connectivity occurs and develops during postnatal blood-brain barrier (BBB) maturation. We demonstrate that mice lacking Cx30 and Cx43 in GFAP (glial fibrillary acidic protein)-positive cells display astrocyte endfeet edema and a partial loss of the astroglial water channel aquaporin-4 and beta-dystroglycan, a transmembrane receptor anchoring astrocyte endfeet to the perivascular basal lamina. Furthermore, the absence of astroglial connexins weakens the BBB, which opens upon increased hydrostatic vascular pressure and shear stress. These results demonstrate that astroglial connexins are necessary to maintain BBB integrity. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 1457-1467; doi: 10.1038/jcbfm.2012.45; published online 4 April 2012