Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.
Neurobiol Aging. 2011 Nov;32(11):2006-15. doi: 10.1016/j.neurobiolaging.2009.12.015. Epub 2009 Dec 31.
The sporadic and familial forms of Creutzfeldt-Jacob disease (sCJD and fCJD) usually appear at older ages (60-70 years and ∼ 50, respectively). Nevertheless, infectious forms such as Kuru and variant CJD (vCJD) present mostly at a much earlier age. To study the effect of age on the pathogenesis of infectious prion disease, we inoculated young and aged mice intraperitoneally with RML prions, followed them to disease end point and studied their disease characteristics. We now show that mice infected at older age present a significantly longer incubation time then mice infected at young age. Additionally, brains of mice infected at older age present significantly less disease-specific pathological markers such as gliosis, vacuolation and PrP(Sc) accumulation. Concomitantly, gene expression analysis revealed that the upregulation of disease-associated inflammatory and stress-response genes, was significantly less pronounced in the brains of mice infected at older age. Based on this data, we suggest that alterations associated with aging, are accountable for the delay in the disease onset and the milder pathology in prion-infected aged mice.
散发性和家族性克雅氏病（sCJD 和 fCJD）通常出现在较年长的年龄（分别为 60-70 岁和 ∼50 岁）。然而，像库鲁病和变异型克雅氏病（vCJD）这样的感染形式通常出现在更早的年龄。为了研究年龄对传染性朊病毒病发病机制的影响，我们通过腹腔内接种 RML 朊病毒使年轻和年老的小鼠感染，然后跟踪至疾病终点，并研究其疾病特征。我们现在表明，感染年龄较大的小鼠潜伏期明显长于感染年龄较小的小鼠。此外，感染年龄较大的小鼠的大脑中，神经胶质增生、空泡形成和 PrP(Sc)聚集等疾病特异性病理标志物的明显减少。同时，基因表达分析表明，感染年龄较大的小鼠大脑中与疾病相关的炎症和应激反应基因的上调程度明显较轻。基于这些数据，我们认为与衰老相关的改变导致了朊病毒感染老年小鼠疾病发作的延迟和较轻的病理。
