Department of Veterinary Science and Public Health, University of Milan, Milan, Italy.
CEA, Italian Reference Laboratory for TSEs, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Turin, Italy.
Life Sci. 2016 Jan 1;144:226-33. doi: 10.1016/j.lfs.2015.12.008. Epub 2015 Dec 3.
In Transmissible Spongiform Encephalopathies (TSEs), the localization of the prion protein in the neuronal membrane lipid rafts (LR) seems to play a role in sustaining the protein misfolding. Changes in membrane properties, due to altered lipid composition, affect their organization and interaction between lipids and protein therein, and consequently also membrane resident protein functionality; dietary polyunsaturated fatty acids (PUFAs), gangliosides and cholesterol seem to influence these processes.
In this work, the influence of administration of different feed, able to change the composition of lipid membrane, on the clinical progression of prion disease was studied.
The activity of three diets (hyperlipidic with 6% fats; hypolipidic with 0.1% fats; and purified with 4% fats) was tested in CD1 mouse model experimentally infected with RML scrapie strain. Presence and distribution of typical central nervous system (CNS) lesions and deposits of PrP(sc) were evaluated by histopathological analysis and immunohistochemistry. Analysis of lipids was performed in homogenate and insoluble brain fraction of the neuronal membrane rich in LR.
Results show that a diet with a different lipid level has not a significant role in the development of the scrapie disease. All infected mice fed with different diets died in the same time span. Histology, immunohistochemistry, and neuropathological analyses of the infected brains did not show significant differences between animals subjected to different diets.
Independently of the diet, the infection induced a significant modification of the lipid composition in homogenates, and a less noticeable one in insoluble brain fraction.
在传染性海绵状脑病（TSEs）中，朊病毒蛋白在神经元膜脂筏（LR）中的定位似乎在维持蛋白质错误折叠中起作用。由于脂质组成的改变，膜特性的变化会影响它们的组织以及其中的脂质和蛋白质之间的相互作用，从而还会影响膜驻留蛋白的功能；膳食多不饱和脂肪酸（PUFAs）、神经节苷脂和胆固醇似乎会影响这些过程。
在这项工作中，研究了给予不同饲料（能够改变脂质膜组成）对朊病毒病临床进展的影响。
在 CD1 小鼠实验感染 RML 瘙痒病株的模型中，测试了三种饮食（高脂血症，含 6%脂肪；低脂血症，含 0.1%脂肪；和纯化，含 4%脂肪）的活性。通过组织病理学分析和免疫组织化学评估典型中枢神经系统（CNS）病变和 PrP(sc)沉积的存在和分布。在富含 LR 的神经元膜的匀浆和不溶性脑部分中进行脂质分析。
结果表明，不同脂质水平的饮食在瘙痒病发展中没有显著作用。用不同饮食喂养的所有感染小鼠在同一时间段内死亡。用不同饮食喂养的感染大脑的组织学、免疫组织化学和神经病理学分析之间没有显示出显著差异。
无论饮食如何，感染都会导致匀浆中脂质组成发生显著改变，而不溶性脑部分的改变则不太明显。
