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Hypercholesterolemia negatively influences morphology and molecular markers of epithelial cells within the choroid plexus in rabbits
Fluids and Barriers of the CNS ( IF 7.3 ) Pub Date : 2020-02-04 , DOI: 10.1186/s12987-020-0175-0
Fumiko Obata 1 , Keishi Narita 2
Affiliation  

Background Choroid plexus (CP) is an important tissue not only to produce cerebrospinal fluid (CSF) but also to regulate substances that are secreted into or absorbed from CSF through blood–cerebrospinal fluid barrier (BCSFB) formed by CP epithelial cells (CPECs). CPECs display signs of deterioration in aged and diseased people. However, whether CPECs in hypercholesterolemic animals develop such damage is not known. Methods We used cholesterol-fed wild-type or Watanabe hereditary hyperlipidemic (WHHL) rabbits of identical age to determine CPEC changes in terms of morphology and protein expression/localization. Results Compared with non-cholesterol-fed control rabbits, prolonged exposure to cholesterol reduced CPEC height and increased lipofuscin levels in CPECs, indicating cellular damage. Expression of aquaporin 1 on the apical membranes of CPECs was diminished in cholesterol-exposed rabbits, implying a reduced CSF-producing function in the CP. The rabbit macrophage-specific antibody (RAM11) immunoreaction became positive in CPECs adjacent to foam cells, indicating an alteration in this cell type. Conclusion Cholesterol insults from the circulation (which is reflected by foam-cell accumulation in the CP) induce CPEC dysfunction, and the latter seems to be enhanced by foam cells in hypercholesterolemic rabbits.

中文翻译:

高胆固醇血症对兔脉络丛内上皮细胞的形态和分子标志物产生负面影响

背景脉络丛(CP)是一种重要的组织,不仅可以产生脑脊液(CSF),还可以调节通过 CP 上皮细胞(CPECs)形成的血脑脊液屏障(BCSFB)向脑脊液中分泌或吸收的物质。CPEC 显示出老年人和患病人群恶化的迹象。然而,高胆固醇血症动物中的 CPEC 是否会产生这种损伤尚不清楚。方法我们使用相同年龄的胆固醇喂养的野生型或渡边遗传性高脂血症 (WHHL) 兔来确定 CPEC 在形态和蛋白质表达/定位方面的变化。结果与非胆固醇喂养的对照兔相比,长期接触胆固醇会降低 CPEC 的高度并增加 CPEC 中的脂褐素水平,表明细胞受损。在暴露于胆固醇的兔子中,CPECs 顶膜上水通道蛋白 1 的表达减少,这意味着 CP 中产生 CSF 的功能降低。兔巨噬细胞特异性抗体 (RAM11) 免疫反应在泡沫细胞附近的 CPEC 中呈阳性,表明这种细胞类型发生了改变。结论 循环中的胆固醇损伤(由 CP 中的泡沫细胞积聚反映)可引起 CPEC 功能障碍,而后者似乎被高胆固醇血症兔的泡沫细胞增强。
更新日期:2020-02-04
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