Ma Lina, Wang Rong, Dong Wen, Li Yun, Xu Baolei, Zhang Jingshuang, Zhao Zhiwei
Department of Geriatrics, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China; Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing 100053, China.
Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing 100053, China.
Behav Brain Res. 2016 Dec 15;315:45-50. doi: 10.1016/j.bbr.2016.07.036. Epub 2016 Jul 21.
Caloric restriction (CR) is the most reliable intervention to extend lifespan and prevent age-related disorders in various species from yeast to rodents. However, the underlying mechanisms have not yet been clearly defined. Therefore, we aimed to identify the underlying mechanisms of long-term CR on age-related learning impairment in C57/BL mice. Thirty six-week-old male C57/BL mice were randomly divided into three groups: normal control group (NC group, n=10), high energy group (HE group, n=10), and CR group (n=10). After 10 months, the Morris water maze test was performed to monitor learning abilities. Western blotting, immunohistochemistry and real-time polymerase chain reaction were used to monitor changes in protein and mRNA levels associated with apoptosis-related proteins in the hippocampus. The average escape latency was lower in the CR group compared with the NC group, and the average time taken to first cross the platform in the CR group was significantly shorter than the HE group. Both Bcl-2 protein and mRNA expression levels in the CR group were significantly higher than those of the NC group and HE group. The expression of Bax, Caspase-3 and PARP protein in the CR group was significantly lower than the NC group. Our findings demonstrate that long-term CR may prevent age-related learning impairments via suppressing apoptosis in mice.
热量限制（CR）是从酵母到啮齿动物等各种物种中延长寿命和预防与年龄相关疾病的最可靠干预措施。然而，其潜在机制尚未明确界定。因此，我们旨在确定长期热量限制对C57/BL小鼠与年龄相关学习障碍的潜在机制。将36只六周龄雄性C57/BL小鼠随机分为三组：正常对照组（NC组，n = 10）、高能组（HE组，n = 10）和热量限制组（CR组，n = 10）。10个月后，进行莫里斯水迷宫试验以监测学习能力。采用蛋白质免疫印迹法、免疫组织化学法和实时聚合酶链反应来监测海马中与凋亡相关蛋白的蛋白质和mRNA水平变化。与NC组相比，CR组的平均逃避潜伏期更低，并且CR组首次穿过平台的平均时间明显短于HE组。CR组中Bcl-2蛋白和mRNA表达水平均显著高于NC组和HE组。CR组中Bax、Caspase-3和PARP蛋白的表达明显低于NC组。我们的研究结果表明，长期热量限制可能通过抑制小鼠凋亡来预防与年龄相关的学习障碍。
