Serrano Carmen, Lyahyai Jaber, Bolea Rosa, Varona Luis, Monleón Eva, Badiola Juan J, Zaragoza Pilar, Martín-Burriel Inmaculada
Laboratorio de Genética Bioquímica (LAGENBIO), Facultad de Veterinaria, Universidad de Zaragoza, Miguel Servet 177, 50013 Zaragoza, Spain.
Vet Res. 2009 Sep-Oct;40(5):42. doi: 10.1051/vetres/2009024. Epub 2009 Apr 30.
Neurodegeneration and gliosis are the main neuropathological features of prion diseases. However, the molecular mechanisms involved in these processes remain unclear. Several studies have demonstrated changes in the expression of apoptotic factors and inflammatory cytokines in animals with experimental infection. Here we present the expression profiles of 15 genes implicated in the intrinsic and extrinsic apoptotic pathways in the central nervous systems of sheep naturally infected with scrapie. Expression changes obtained by real-time RT-PCR were also compared with the extent of classical scrapie lesions, such as prion deposition, neuronal vacuolisation, spongiosis, and astrogliosis as well as with the activation of caspase-3, using a stepwise regression. The results suggest that the factors assessed participate in apoptotic or inflammatory functions, depending on the affected area. The mitochondrial apoptosis pathway was associated with prion deposition in the prefrontal cortex (the less affected area), and with activation of caspase-3-mediated cell death via over-expression of BAK. In addition to its known association with astroglial activation, the extrinsic apoptosis pathway was also related to cell death and neuronal vacuolisation.
神经退行性变和胶质细胞增生是朊病毒病的主要神经病理学特征。然而，这些过程所涉及的分子机制仍不清楚。多项研究已证明实验感染动物中凋亡因子和炎性细胞因子的表达发生了变化。在此，我们展示了自然感染羊瘙痒病的绵羊中枢神经系统中15个与内源性和外源性凋亡途径相关基因的表达谱。通过实时逆转录聚合酶链反应获得的表达变化，还与经典羊瘙痒病病变的程度进行了比较，如朊病毒沉积、神经元空泡化、海绵状变性和星形胶质细胞增生，以及与半胱天冬酶-3的激活情况进行了比较，采用逐步回归分析。结果表明，所评估的这些因子根据受影响的区域参与凋亡或炎症功能。线粒体凋亡途径与额叶皮质（受影响较小的区域）中的朊病毒沉积有关，并与通过BAK的过度表达激活半胱天冬酶-3介导的细胞死亡有关。除了其与星形胶质细胞激活的已知关联外，外源性凋亡途径还与细胞死亡和神经元空泡化有关。
