Departments of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
J Alzheimers Dis. 2012;30(3):573-83. doi: 10.3233/JAD-2012-120112.
Senescence-accelerated mice 8 (SAMP8), a model of aging, display many established pathological features of Alzheimer's disease (AD); however, whether cell cycle alterations exist in these animals remains unknown. Given that these animals present changes such as tau phosphorylation and redox imbalance, both associated with cell cycle alterations, we determined whether changes in cell cycle markers were present in SAMP8 and SAMR1 (control strain) at 3, 6, and 9 months-old brains. As expected, an increase in tau hyperphosphorylation and its associated machinery, i.e., cdk5 and GSK3β, was observed both between strains and also with aging. Particularly, significant differences in cyclin A, cyclin D1, cyclin E, Cdk2, cyclin B, pR, and E2F1 were found when comparing SAMP8 to SAMR1. More interestingly, a partial correlation with several cell cycle markers described in AD brain is found in SAMP8, indicating that some specific hallmarks of AD are also present in this strain, which has been postulated as an early switch model of the disease.
衰老加速小鼠 8 （SAMP8）是一种衰老模型，表现出许多阿尔茨海默病（AD）的既定病理特征；然而，这些动物是否存在细胞周期改变尚不清楚。鉴于这些动物存在与细胞周期改变相关的tau 磷酸化和氧化还原失衡等变化，我们确定了在 3、6 和 9 个月大的 SAMP8 和 SAMR1（对照品系）大脑中是否存在细胞周期标志物的变化。正如预期的那样，tau 过度磷酸化及其相关机制（即-cdk5 和 GSK3β）在两种品系之间以及随年龄增长均有增加。特别是，当比较 SAMP8 和 SAMR1 时，发现 cyclin A、cyclin D1、cyclin E、Cdk2、cyclin B、pR 和 E2F1 存在显著差异。更有趣的是，在 SAMP8 中发现了与 AD 大脑中描述的一些细胞周期标志物的部分相关性，表明该品系也存在 AD 的一些特定特征，这被认为是该疾病的早期开关模型。
