Department of Biomedical Science and Technology, University of Cagliari, 09042-Monserrato, Italy.
Lipids Health Dis. 2011 Aug 4;10:132. doi: 10.1186/1476-511X-10-132.
Cholesterol changes have been described in prion-cell models and in experimental rodent scrapie; yet, the pattern of this association is still controversial.
To shed light on the matter, we analysed and compared cholesterol variations in ScN2a cells and in brains of Scrapie-infected C57Bl/6 mice, using two different methods: a fluorimetric-enzymatic cholesterol assay, and high performance liquid chromatography-mass spectroscopy (HPLC-MS).
Compared to uninfected controls, similar cholesterol metabolism anomalies were observed in infected cells and brains by both methods; however, only HPLC-MS revealed statistically significant cholesterol variations, particularly in the cholesteryl esters (CE) fraction. HPLC-MS analyses also revealed different fatty acid composition of the CE fraction in cells and brains. In N2a cells, their profile reflected that of serum, while in normal brains cholesteryl-linoleate only was found at detectable levels. Following prion infection, most CE species were increased in the CE pool of ScN2a cells, whereas a conspicuous amount of cholesteryl-arachidonate only was found to contribute to the cerebral increase of CE. Of interest, oral pravastatin administration to Scrapie-infected mice, was associated with a significant reduction of cerebral free cholesterol (FC) along with a concomitant further increase of the CE pool, which included increased amounts of both cholesteryl-linoleate and cholesteryl-arachidonate.
Although mechanistic studies are needed to establish the pathophysiological relevance of changes in cerebral CE concentrations, to the best of our knowledge this is the first report to provide evidence of increased cholesterol esterification in brains of prion-infected mice, untreated and treated with pravastatin.
已在朊病毒细胞模型和实验性啮齿动物瘙痒病中描述了胆固醇变化；然而，这种关联的模式仍存在争议。
为了阐明这一问题，我们使用两种不同的方法分析和比较了 ScN2a 细胞和感染瘙痒病的 C57Bl/6 小鼠脑中的胆固醇变化：荧光酶法胆固醇测定法和高效液相色谱-质谱联用（HPLC-MS）。
与未感染对照相比，两种方法均观察到感染细胞和大脑中的胆固醇代谢异常相似；然而，只有 HPLC-MS 揭示了统计学上显著的胆固醇变化，特别是在胆固醇酯（CE）部分。HPLC-MS 分析还揭示了细胞和大脑中 CE 部分的不同脂肪酸组成。在 N2a 细胞中，其谱反映了血清的谱，而在正常大脑中仅发现可检测水平的胆固醇亚麻酸酯。在朊病毒感染后，大多数 CE 物种在 ScN2a 细胞的 CE 池中增加，而仅发现大量的胆固醇花生四烯酸有助于大脑中 CE 的增加。有趣的是，普伐他汀对瘙痒病感染小鼠的口服给药与大脑游离胆固醇（FC）的显著减少有关，同时 CE 池进一步增加，其中包括胆固醇亚麻酸酯和胆固醇花生四烯酸的含量增加。
尽管需要进行机制研究以确定脑 CE 浓度变化的病理生理学相关性，但据我们所知，这是首次报道提供未经处理和用普伐他汀处理的感染瘙痒病的小鼠脑中胆固醇酯化增加的证据。
