Lippoldt A, Jansson A, Kniesel U, Andbjer B, Andersson A, Wolburg H, Fuxe K, Haller H
Max Delbrück-Center for Molecular Medicine, Berlin-Buch, Germany.
Brain Res. 2000 Jan 31;854(1-2):197-206. doi: 10.1016/s0006-8993(99)02355-0.
The molecular composition and functional properties of cell-cell junctions of choroid plexus epithelial cells and the ependyma of the lateral ventricular wall were investigated in the rat brain. Expression studies of cadherin and alpha- and beta-catenins, as well as expression of occludin and ZO-1, indicated that cell adherens and tight junctions were present in both choroid plexus epithelial cells and in ependymal cells. We then tested the hypothesis that phorbolester in vivo can induce changes in the expression level of adherens and tight junction molecules at the blood-cerebrospinal fluid (CSF) barrier as well as in the ependyma. In addition, the functional properties of the ependymal junctions were tested by injection of dextran 3000 into the striatum after phorbolester application. Twenty-four hours after phorbolester-injection into the lateral ventricle of the rat brain, the expression patterns of tight and adherens junction molecules were markedly changed in the epithelial cells of the choroid plexus. The adherens junction proteins cadherin and beta-catenin were reduced in both the ependymal cells of the lateral ventricle and choroid plexus epithelial cells. In addition, the occludin-immunoreactivity of the choroid plexus epithelial cells was strongly reduced. However, the ZO-1 immunoreactivity was not affected by the phorbol ester-treatment and the alpha-catenin immunoreactivity was not changed. Furthermore, phorbol ester injection induced a reduction of the volume of intrastriatal injected biotinylated dextran (m.w. 3000), which is consistent with a modulatory influence of protein kinase C activation on the clearance capacity of the brain.
在大鼠脑中研究了脉络丛上皮细胞与侧脑室壁室管膜细胞间细胞连接的分子组成和功能特性。钙黏蛋白、α-连环蛋白和β-连环蛋白的表达研究,以及闭合蛋白和ZO-1的表达研究表明,脉络丛上皮细胞和室管膜细胞中均存在黏着连接和紧密连接。然后,我们检验了以下假设:体内佛波酯可诱导血脑脊液(CSF)屏障以及室管膜中黏着连接和紧密连接分子表达水平的变化。此外,在应用佛波酯后,通过向纹状体注射葡聚糖3000来测试室管膜连接的功能特性。向大鼠脑侧脑室注射佛波酯24小时后,脉络丛上皮细胞中紧密连接和黏着连接分子的表达模式发生了显著变化。侧脑室室管膜细胞和脉络丛上皮细胞中的黏着连接蛋白钙黏蛋白和β-连环蛋白均减少。此外,脉络丛上皮细胞的闭合蛋白免疫反应性显著降低。然而,ZO-1免疫反应性不受佛波酯处理的影响,α-连环蛋白免疫反应性也未改变。此外,佛波酯注射导致纹状体内注射的生物素化葡聚糖(分子量3000)体积减少,这与蛋白激酶C激活对脑清除能力的调节作用一致。