Age-related alterations affect the susceptibility of mice to prion infection
Age-related alterations affect the susceptibility of mice to prion infection
复制标题
DOI：
10.1016/j.neurobiolaging.2009.12.015
复制
发表时间：
2011-11-01
影响因子：
4.2
通讯作者：
Gabizon, Ruth
中科院分区：
文献类型：
--
作者：
Avrahami, Dana;Gabizon, Ruth
散发性和家族性克雅氏病（sCJD和fCJD）通常出现在老年人（分别为60-70岁和50岁左右）。然而，传染性形式，如库鲁病和变异型CJD （vCJD）大多出现在更早的年龄。为了研究年龄对感染性朊病毒病发病机制的影响，我们分别给幼龄和老年小鼠腹腔注射RML朊病毒，随访至疾病终点，研究其疾病特征。我们现在表明，老年感染的小鼠比幼年感染的小鼠潜伏期明显更长。此外，老年感染小鼠的大脑出现的疾病特异性病理标志物（如胶质细胞增生、空泡形成和PrP（Sc）积累）明显减少。同时，基因表达分析显示，在老年感染的小鼠大脑中，与疾病相关的炎症和应激反应基因的上调明显不那么明显。基于这些数据，我们认为与衰老相关的改变是朊病毒感染老年小鼠疾病发病延迟和病理较轻的原因。(C) 2009爱思唯尔公司版权所有。
The sporadic and familial forms of Creutzfeldt-Jacob disease (sCJD and fCJD) usually appear at older ages (60-70 years and similar to 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. (C) 2009 Elsevier Inc. All rights reserved.