Laboratorio de Genética Bioquímica (LAGENBIO), Universidad de Zaragoza, Instituto Agroalimentario de Aragón-IA2, Instituto de Investigación Sanitaria Aragón-IISA, 50013 Zaragoza, Spain.
Centro de Encefalopatías y Enfermedades Transmisibles Emergentes (CEETE), Universidad de Zaragoza, Instituto Agroalimentario de Aragón-IA2, Instituto de Investigación Sanitaria Aragón-IISA, 50013 Zaragoza, Spain.
Biomolecules. 2020 May 2;10(5):706. doi: 10.3390/biom10050706.
Prion diseases affect both animals and humans. Research in the natural animal model of the disease could help in the understanding of neuropathological mechanisms and in the development of biomarkers for human pathologies. For this purpose, we studied the expression of 10 genes involved in prion propagation in vitro in the central nervous system of scrapie-infected sheep. Dysregulated genes ( and ) were further analysed in a transgenic murine model (Tg338) of scrapie, and their protein distribution was determined using immunohistochemistry and Western blot. Their potential as biomarkers was finally assessed using enzyme-linked immunosorbent assay (ELISA) in cerebrospinal fluid (CSF) of scrapie sheep and Creutzfeldt-Jakob disease (CJD) patients. Protein BAMBI was upregulated in highly affected brain areas and CHGA was overexpressed along the brain in both models. Moreover, BAMBI and CHGA immunostaining scores strongly correlated with spongiosis and microgliosis in mice. Finally, levels of BAMBI were significantly higher in the CSF of clinical sheep and CJD patients. In addition to their potential as biomarkers, our work confirms the role of BAMBI and CHGA in prion neuropathology in vivo, but besides prion replication, they seem to be involved in the characteristic neuroinflammatory response associated to prion infection.
朊病毒病影响动物和人类。对疾病自然动物模型的研究有助于了解神经病理学机制，并开发人类病理学的生物标志物。为此，我们研究了朊病毒在体外感染绵羊中枢神经系统中 10 个与朊病毒传播相关基因的表达。在朊病毒感染的转基因小鼠模型（Tg338）中进一步分析失调基因（和），并使用免疫组织化学和 Western blot 确定其蛋白分布。最后，使用酶联免疫吸附测定法（ELISA）在朊病毒感染绵羊和克雅氏病（CJD）患者的脑脊液（CSF）中评估其作为生物标志物的潜力。在高度受影响的脑区中，蛋白 BAMBI 上调，在两个模型中 CHGA 沿脑过度表达。此外，BAMBI 和 CHGA 免疫染色评分与小鼠的海绵状变性和小胶质细胞增生强烈相关。最后，在临床绵羊和 CJD 患者的 CSF 中，BAMBI 水平显著升高。除了作为生物标志物的潜力外，我们的工作还证实了 BAMBI 和 CHGA 在体内朊病毒神经病理学中的作用，但除了朊病毒复制外，它们似乎还参与了与朊病毒感染相关的特征性神经炎症反应。
