The most important risk factor for the development of sporadic Alzheimer’s disease (AD) is ageing. Senescence accelerated mouse prone 8 (SAMP8) is a model of sporadic AD, with senescence accelerated resistant mouse (SAMR1) as a control. In this study, we aimed to determine the onset of senescence-induced neurodegeneration and the related potential therapeutic window using behavioral experiments, immunohistochemistry and western blotting in SAMP8 and SAMR1 mice at 3, 6 and 9 months of age. The Y-maze revealed significantly impaired working spatial memory of SAMP8 mice from the 6^th month. With ageing, increasing plasma concentrations of proinflammatory cytokines in SAMP8 mice were detected as well as significantly increased astrocytosis in the cortex and microgliosis in the brainstem. Moreover, from the 3^rd month, SAMP8 mice displayed a decreased number of neurons and neurogenesis in the hippocampus. From the 6^th month, increased pathological phosphorylation of tau protein at Thr231 and Ser214 was observed in the hippocampi of SAMP8 mice. In conclusion, changes specific for neurodegenerative processes were observed between the 3^rd and 6^th month of age in SAMP8 mice; thus, potential neuroprotective interventions could be applied between these ages.

中文翻译：

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SAMP8 小鼠中年龄相关的代谢和神经退行性变化


发生散发性阿尔茨海默病（AD）的最重要的危险因素是衰老。衰老加速小鼠倾向 8 (SAMP8) 是散发性 AD 模型，以衰老加速抗性小鼠 (SAMR1) 作为对照。在这项研究中，我们旨在通过 3、6 和 9 个月龄 SAMP8 和 SAMR1 小鼠的行为实验、免疫组织化学和蛋白质印迹来确定衰老诱导的神经变性的发作以及相关的潜在治疗窗口。 Y 迷宫显示 SAMP8 小鼠的工作空间记忆从第 6^个月开始显着受损。随着年龄的增长，SAMP8 小鼠中促炎细胞因子的血浆浓度增加，皮质中的星形细胞增多和脑干中的小胶质细胞增多。此外，从第3^个月开始，SAMP8小鼠的海马神经元数量和神经发生减少。从第6^个月开始，在SAMP8小鼠的海马中观察到tau蛋白Thr231和Ser214病理性磷酸化增加。总之，在 SAMP8 小鼠的第 3^个月和第 6^个月之间观察到神经退行性过程特有的变化；因此，可以在这些年龄段之间应用潜在的神经保护干预措施。