Neuronal Cell Cycle Re-Entry Markers are Altered in the Senescence Accelerated Mouse P8 (SAMP8)
Neuronal Cell Cycle Re-Entry Markers are Altered in the Senescence Accelerated Mouse P8 (SAMP8)
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DOI：
10.3233/jad-2012-120112
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发表时间：
2012-01-01
影响因子：
4
通讯作者：
Pallas, Merce
中科院分区：
文献类型：
--
作者：
Casadesus, Gemma;Gutierrez-Cuesta, Javier;Pallas, Merce
衰老加速小鼠8号(SAMP8)是一种衰老模型，表现出许多阿尔茨海默病(AD)的病理特征；然而，这些动物中是否存在细胞周期变化尚不清楚。鉴于这些动物存在tau磷酸化和氧化还原失衡等变化，两者都与细胞周期变化有关，我们确定了3、6和9个月大的SAMP8和SAMR1(对照品系)中是否存在细胞周期标志物的变化。正如预期的那样，tau蛋白过度磷酸化及其相关机制，即CDK5和GSK3β，在菌株之间以及随着年龄的增长都观察到了增加。特别是SAMP8和SAMR1相比，细胞周期蛋白A、细胞周期蛋白D1、细胞周期蛋白E、细胞周期蛋白CDK2、细胞周期蛋白B、Pr和E2F1均有显著差异。更有趣的是，在SAMP8中发现了与AD脑中描述的几个细胞周期标记物的部分相关性，表明这种菌株也存在AD的一些特定特征，它被假设为疾病的早期开关模型。
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 GSK3 beta, 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.