Yan Wen-Wen, Chen Gui-Hai, Wang Fang, Tong Jing-Jing, Tao Fei
Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, PR China.
Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, PR China; Department of Neurology, The First People׳s Hospital of Chenzhou, Southern Medical University, Chenzhou 423000, Hunan Province, PR China.
Brain Res. 2015 Apr 7;1603:22-31. doi: 10.1016/j.brainres.2015.01.042. Epub 2015 Jan 31.
Age-associated memory impairment (AAMI) not only reduces the quality of life for the elderly but also increases the costs of healthcare for society. Methods that can regulate glucose metabolism, insulin/insulin-like growth factor 1 (IGF-1) system and acetylated histone H4 lysine 8 (H4K8ac), one of the most well-researched facets of histone acetylation modification associating with cognition, tend to ameliorate the AAMI. Here, we used SAMP8 mice, the excellent animal model of aging and AAMI, to study the effect of long-term treatment with acarbose, an inhibitor of a-glucosidase, on AAMI and explore whether blood glucose, insulin/IGF-1 system and H4K8ac are associated with potential effects. The treatment group received acarbose (20mg/kg/d, dissolved in drinking water) at the age of 3-month until 9-month old before the behavioral test, and the controls only received water. Compared to the young controls (3-month-old, n=11), the old group (9-month-old, n=8) had declined abilities of spatial learning and memory and levels of serum insulin, hippocampal insulin receptors (InsRs) and H4K8ac. Interestingly, the acarbose group (9-month-old, n=9) showed better abilities of spatial learning and memory and higher levels of insulin, InsRs and H4K8ac relative to the old controls. Good performance of spatial learning and memory was positively correlated with the elevated insulin, InsRs and H4K8ac. All these results suggested that long-term administration of acarbose could alleviate the age-related impairment of spatial learning and memory in the SAMP8 mice, and the alleviated reduction of an insulin system and H4K8ac might be associated with the alleviation.
年龄相关性记忆损害（AAMI）不仅降低了老年人的生活质量，还增加了社会的医疗保健成本。能够调节葡萄糖代谢、胰岛素/胰岛素样生长因子1（IGF-1）系统以及乙酰化组蛋白H4赖氨酸8（H4K8ac）（与认知相关的组蛋白乙酰化修饰研究最多的方面之一）的方法，往往能改善AAMI。在此，我们使用SAMP8小鼠（衰老和AAMI的优秀动物模型）来研究α-葡萄糖苷酶抑制剂阿卡波糖长期治疗对AAMI的影响，并探讨血糖、胰岛素/IGF-1系统和H4K8ac是否与潜在作用相关。治疗组在3月龄至9月龄行为测试前接受阿卡波糖（20mg/kg/d，溶于饮用水中），对照组仅接受水。与年轻对照组（3月龄，n = 11）相比，老年组（9月龄，n = 8）的空间学习和记忆能力以及血清胰岛素、海马胰岛素受体（InsRs）和H4K8ac水平均下降。有趣的是，与老年对照组相比，阿卡波糖组（9月龄，n = 9）表现出更好的空间学习和记忆能力以及更高的胰岛素、InsRs和H4K8ac水平。空间学习和记忆的良好表现与胰岛素、InsRs和H4K8ac的升高呈正相关。所有这些结果表明，长期给予阿卡波糖可减轻SAMP8小鼠与年龄相关的空间学习和记忆损害，胰岛素系统和H4K8ac的减轻可能与这种改善有关。
