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紧密连接蛋白的差异分布表明,成年小鼠大脑中的 tanycytes 在血脑屏障调节中发挥作用。

Differential distribution of tight junction proteins suggests a role for tanycytes in blood-hypothalamus barrier regulation in the adult mouse brain.

机构信息

Jean-Pierre Aubert Research Center, Development and Plasticity of the Postnatal Brain, Inserm U837, 59045 Lille Cedex, France.

出版信息

J Comp Neurol. 2010 Apr 1;518(7):943-62. doi: 10.1002/cne.22273.

Abstract

The median eminence is one of the seven so-called circumventricular organs. It is located in the basal hypothalamus, ventral to the third ventricle and adjacent to the arcuate nucleus. This structure characteristically contains a rich capillary plexus and features a fenestrated endothelium, making it a direct target of blood-borne molecules. The median eminence also contains highly specialized ependymal cells called tanycytes, which line the floor of the third ventricle. It has been hypothesized that one of the functions of these cells is to create a barrier that prevents substances in the portal capillary spaces from entering the brain. In this paper, we utilize immunohistochemistry to study the expression of tight junction proteins in the cells that compose the median eminence in adult mice. Our results indicate that tanycytes of the median eminence express occludin, ZO-1, and claudin 1 and 5, but not claudin 3. Remarkably, these molecules are organized as a continuous belt around the cell bodies of the tanycytes that line the ventral part of the third ventricle. In contrast, the tanycytes at the periphery of the arcuate nucleus do not express claudin 1 and instead exhibit a disorganized expression pattern of occludin, ZO-1, and claudin 5. Consistent with these observations, permeability studies using peripheral or central injections of Evans blue dye show that only the tanycytes of the median eminence are joined at their apices by functional tight junctions, whereas tanycytes located at the level of the arcuate nucleus form a permeable layer. In conclusion, this study reveals a unique expression pattern of tight junction proteins in hypothalamic tanycytes, which yields new insights into their barrier properties.

摘要

正中隆起是所谓的七个室周器官之一。它位于下丘脑底部,第三脑室腹侧,与弓状核相邻。该结构特征性地包含丰富的毛细血管丛,并具有有孔的内皮,使其成为血液来源分子的直接靶标。正中隆起还包含高度特化的室管膜细胞,称为室管膜下细胞,它们排列在第三脑室的底部。有人假设这些细胞的功能之一是形成一种屏障,防止门脉毛细血管空间中的物质进入大脑。在本文中,我们利用免疫组织化学研究成年小鼠正中隆起细胞中紧密连接蛋白的表达。我们的结果表明,正中隆起的室管膜下细胞表达闭合蛋白、ZO-1 和 Claudin1 和 5,但不表达 Claudin3。值得注意的是,这些分子在排列在第三脑室腹侧的室管膜下细胞的细胞体周围形成一个连续的带。相比之下,弓状核周围的室管膜下细胞不表达 Claudin1,而是表现出闭合蛋白、ZO-1 和 Claudin5 的紊乱表达模式。与这些观察结果一致,使用外周或中央注射 Evans 蓝染料的通透性研究表明,只有正中隆起的室管膜下细胞在其顶端通过功能性紧密连接连接,而位于弓状核水平的室管膜下细胞形成一个可渗透的层。总之,这项研究揭示了下丘脑室管膜下细胞中紧密连接蛋白的独特表达模式,为它们的屏障特性提供了新的见解。

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