Department of Molecular Pathology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Department of Anatomy and Cell Biology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Fluids Barriers CNS. 2020 Feb 4;17(1):13. doi: 10.1186/s12987-020-0175-0.
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.
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.
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.
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.
脉络丛（CP）不仅是产生脑脊液（CSF）的重要组织，而且还通过 CP 上皮细胞（CPECs）形成的血脑脊液屏障（BCSFB）调节分泌或从 CSF 中吸收的物质。CPECs 在老年和患病人群中表现出恶化的迹象。然而，尚不清楚高胆固醇血症动物中的 CPECs 是否会发生这种损伤。
我们使用相同年龄的胆固醇喂养的野生型或 Watanabe 遗传性高脂血症（WHHL）兔子来确定 CPEC 在形态和蛋白质表达/定位方面的变化。
与未喂食胆固醇的对照兔子相比，长时间暴露于胆固醇会降低 CPEC 的高度并增加 CPECs 中的脂褐素水平，表明细胞损伤。胆固醇暴露的兔子中 CP 上皮细胞顶膜上的水通道蛋白 1 的表达减少，表明 CSF 产生功能降低。兔巨噬细胞特异性抗体（RAM11）免疫反应在泡沫细胞附近的 CPECs 中呈阳性，表明该细胞类型发生了改变。
循环中的胆固醇（通过 CP 中泡沫细胞的积累来反映）会引起 CPEC 功能障碍，而在高胆固醇血症兔子中，泡沫细胞似乎会增强这种功能障碍。
