Wang Xin, Meng Zhao-Xiang, Chen Ying-Zhu, Li Yu-Ping, Zhou Hong-Yu, Yang Man, Zhao Ting-Ting, Gong Yu-Lai, Wu Yi, Liu Tao
Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai; Department of Rehabilitation, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China.
Department of Rehabilitation, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China.
Neural Regen Res. 2020 Dec;15(12):2327-2334. doi: 10.4103/1673-5374.285005.
The mechanisms of age-associated memory impairment may be associated with glutamate receptor function and chromatin modification. To observe the effect of an enriched environment on the cognitive function of mice with age-associated memory impairment, 3-month-old C57BL/6 male mice ("young" mice) were raised in a standard environment, while 24-month-old C57BL/6 male mice with memory impairment ("age-associated memory impairment" mice) were raised in either a standard environment or an enriched environment. The enriched environment included a variety of stimuli involving movement and sensation. A water maze test was then used to measure cognitive function in the mice. Furthermore, quantitative real-time polymerase chain reaction and western blot assays were used to detect right hippocampal GluN2B mRNA as well as protein expression of GluN2B and CREB binding protein in all mice. In addition, chromatin immunoprecipitation was used to measure the extent of histone acetylation of the hippocampal GluN2B gene promoters. Compared with the young mice, the water maze performance of age-associated memory impairment mice in the standard environment was significantly decreased. In addition, there were significantly lower levels of total histone acetylation and expression of CREB binding protein in the hippocampus of age-associated memory impairment mice in the standard environment compared with the young mice. There were also significantly lower levels of histone acetylation, protein expression, and mRNA expression of GluN2B in the hippocampus of these mice. In contrast, in the age-associated memory impairment mice with the enriched environment intervention, the water maze performance and molecular biological indexes were significantly improved. These data confirm that an enriched environment can improve cognitive dysfunction in age-associated memory impairment mice, and suggest that the mechanisms may be related to the increased expression of CREB binding protein and the increased degree of total histone acetylation in the hippocampus of age-associated memory impairment mice, which may cause the increase of histone acetylation of GluN2B gene promoter and the enhancement of GluN2B mRNA transcription and protein expression in hippocampus. The animal experiment was approved by the Animal Ethics Committee of Yangzhou University, China (approval No. 20170312001) in March 2017.
与年龄相关的记忆障碍机制可能与谷氨酸受体功能和染色质修饰有关。为观察丰富环境对伴有年龄相关记忆障碍小鼠认知功能的影响，将3月龄C57BL/6雄性小鼠（“年轻”小鼠）饲养于标准环境中，而将24月龄伴有记忆障碍的C57BL/6雄性小鼠（“年龄相关记忆障碍”小鼠）饲养于标准环境或丰富环境中。丰富环境包括各种涉及运动和感觉的刺激。然后使用水迷宫试验来测量小鼠的认知功能。此外，采用定量实时聚合酶链反应和蛋白质免疫印迹分析检测所有小鼠右侧海马GluN2B mRNA以及GluN2B和CREB结合蛋白的蛋白表达。另外，采用染色质免疫沉淀法测量海马GluN2B基因启动子的组蛋白乙酰化程度。与年轻小鼠相比，标准环境中年龄相关记忆障碍小鼠的水迷宫表现显著降低。此外，与年轻小鼠相比，标准环境中年龄相关记忆障碍小鼠海马中的总组蛋白乙酰化水平和CREB结合蛋白表达显著降低。这些小鼠海马中GluN2B的组蛋白乙酰化水平、蛋白表达和mRNA表达也显著降低。相反，在接受丰富环境干预的年龄相关记忆障碍小鼠中，水迷宫表现和分子生物学指标显著改善。这些数据证实丰富环境可改善年龄相关记忆障碍小鼠的认知功能障碍，并表明其机制可能与年龄相关记忆障碍小鼠海马中CREB结合蛋白表达增加和总组蛋白乙酰化程度增加有关，这可能导致GluN2B基因启动子的组蛋白乙酰化增加以及海马中GluN2B mRNA转录和蛋白表达增强。该动物实验于2017年3月获得中国扬州大学动物伦理委员会批准（批准号：20170312001）。
