Lafarga M, Crespo P, Berciano M T, Andres M A, Leon J
Department of Anatomy and Cell Biology, Faculty of Medicine, University of Cantabria, Santander, Spain.
Brain Res Mol Brain Res. 1994 Jan;21(1-2):115-23. doi: 10.1016/0169-328x(94)90384-0.
We have studied the expression of apolipoprotein E (ApoE) mRNA in the cerebella of control and experimental rabbits fed with a cholesterol-rich diet for 8 weeks. Cholesterol-treated rabbits show a dramatic increase in serum cholesterol levels; however, no significant variations in the expression level of cerebellar ApoE mRNA were found in comparison to control rabbits. In addition, no differences were observed between control and hypercholesterolemic rabbits in the in situ hybridization pattern of ApoE mRNA on cerebellar cortex sections. ApoE mRNA was localized in astroglial processes associated with Purkinje cell bodies and dendrites, granule cell clusters, blood vessels and nerve fibers of the white matter. No expression of ApoE mRNA was observed in Purkinje and granule cell neurons. Polarized light examination of cryostat cerebellar sections revealed the absence of cholesterol-rich microglia/macrophage cells induced by the hypercholesterolemia. In this way, neither reactive microglial cells nor perivascular phagocytes were found by ultrastructural analysis in hypercholesterolemic conditions. The pattern of glial fibrillary acidic protein of the astroglial cells of the cerebellar cortex as well as their nuclear size were unchanged following cholesterol treatment, indicating the absence of astroglial activation induced by hypercholesterolemia. Our results suggest that cerebellar ApoE does not contribute to the general cholesterol homeostasis outside of the brain and supports the view that this cerebellar ApoE is involved in paracrine and autocrine functions particularly related with synapse turnover and membrane remodelling of astroglial cells.
我们研究了喂食富含胆固醇饮食8周的对照兔和实验兔小脑载脂蛋白E（ApoE）mRNA的表达。胆固醇处理的兔子血清胆固醇水平显著升高；然而，与对照兔相比，小脑ApoE mRNA的表达水平未发现显著变化。此外，在小脑皮质切片上，对照兔和高胆固醇血症兔之间ApoE mRNA的原位杂交模式没有差异。ApoE mRNA定位于与浦肯野细胞体和树突、颗粒细胞簇、血管及白质神经纤维相关的星形胶质细胞突起中。在浦肯野细胞和颗粒细胞神经元中未观察到ApoE mRNA的表达。对冷冻切片的小脑进行偏振光检查发现，没有由高胆固醇血症诱导的富含胆固醇的小胶质细胞/巨噬细胞。这样，在高胆固醇血症条件下，通过超微结构分析未发现反应性小胶质细胞和血管周围吞噬细胞。胆固醇处理后，小脑皮质星形胶质细胞的胶质纤维酸性蛋白模式及其核大小未改变，表明不存在由高胆固醇血症诱导的星形胶质细胞活化。我们的结果表明，小脑ApoE对脑外的总体胆固醇稳态没有贡献，并支持这样的观点，即这种小脑ApoE参与旁分泌和自分泌功能，特别是与星形胶质细胞的突触更新和膜重塑相关。
