National Veterinary Research Institute, Partyzantow 57, 24-100 Pulawy, Poland; Centro de Investigación en Sanidad Animal (CISA), INIA, 28130 Valdeolmos, Madrid, Spain.
National Veterinary Research Institute, Partyzantow 57, 24-100 Pulawy, Poland.
Brain Res. 2010 Sep 10;1351:13-22. doi: 10.1016/j.brainres.2010.07.035. Epub 2010 Jul 21.
Since 2004 cases of atypical bovine spongiform encephalopathy (BSE) in older cattle are recorded on the basis of aberrant glycoprofiles of prion protein resistant to proteolysis (PrP(res)). The nature of those types of PrP(res) is still not fully understood but the epidemiological data indicate that their occurrence is rare. Hitherto, most BSE cases were studied on the basis of the features of pathological form of prion protein (PrP(Sc)) or lesions observed in the gray matter of the brain. Here we propose the gene expression profiling as a method to characterize and distinguish BSE types. Thus, the aim of the study was to compare the activity of some genes which are known to play a role in the pathogenesis of transmissible spongiform encephalopathies (TSEs). Significant differences in the expression level of the selected genes in the brain stem were observed for 7 out of 11 genes tested when the results for BSE affected and healthy control animals were compared. Significant up-regulation of caspase 3, Bax and 14-3-3 protein encoding genes was apparent in the obex of all BSE affected cattle regardless of the prion type. Significant and unique to BSE H-type up-regulation was detected in prion and SOD1 genes, while BSE C-type was characterized by higher Bcl-2 and Fyn gene expression levels in respect to other BSE types and control animals. Different gene expression profiles of bovine brains infected with classical and atypical BSE indicate possible different pathogenesis or origin of the disease.
自 2004 年以来,根据对蛋白酶抗性朊病毒蛋白(PrP(res))异常糖基化图谱的记录,在老牛中发现了非典型牛海绵状脑病(BSE)病例。这些类型的 PrP(res)的性质仍不完全清楚,但流行病学数据表明其发生频率很低。迄今为止,大多数 BSE 病例都是基于朊病毒蛋白(PrP(Sc))的病理形态特征或大脑灰质中观察到的病变进行研究的。在这里,我们提出基因表达谱分析作为一种表征和区分 BSE 类型的方法。因此,本研究的目的是比较一些已知在传染性海绵状脑病(TSEs)发病机制中起作用的基因的活性。当比较受影响的 BSE 动物和健康对照动物的结果时,在 11 个测试基因中,有 7 个在脑干中观察到所选基因的表达水平存在显著差异。在所有受 BSE 影响的牛的 obex 中,caspase 3、Bax 和 14-3-3 蛋白编码基因的显著上调是明显的,而与其他 BSE 类型和对照动物相比,BSE H 型的显著上调是独特的。在 PrP 和 SOD1 基因中检测到 BSE C 型的独特上调,而 Bcl-2 和 Fyn 基因的表达水平较高,这表明 BSE C 型与其他 BSE 类型和对照动物相比具有更高的表达水平。感染经典和非典型 BSE 的牛脑的不同基因表达谱表明,疾病的发病机制或起源可能不同。