Tong Jing-Jing, Chen Gui-Hai, Wang Fang, Li Xue-Wei, Cao Lei, Sui Xu, Tao Fei, Yan Wen-Wen, Wei Zhao-Jun
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; School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei 230009, PR China.
Behav Brain Res. 2015 May 1;284:138-52. doi: 10.1016/j.bbr.2015.01.052. Epub 2015 Feb 16.
The administration of maintaining the homeostasis of insulin/insulin-like growth factor 1 (IGF-1) signaling and/or glucose metabolism may reverse brain aging. In the present study, we investigated the effect of acarbose, an inhibitor of α-glucosidase, on age-related behavioral and biochemical changes. The SAMP8 mice were randomly divided into old control group and acarbose-treatment group. The mice in the acarbose group were administered acarbose (20 mg/kg/d, dissolved in drinking water) orally from 3 to 9 months of age when a new group of 3-month-old mice was added as young controls. The results showed that the aged controls exhibited declines in sensorimotor ability, open field anxiety, spatial and non-spatial memory abilities, decreased serum insulin levels, increased IGF-1 receptor and synaptotagmin 1 (Syt1) levels and decreased insulin receptor, brain-derived neurotrophic factor (BDNF) and syntaxin 1 (Stx1) levels in the hippocampal layers. The age-related behavioral deficits correlated with the serological and histochemical data. Chronic acarbose treatment relieved these age-related changes, especially with respect to learning and memory abilities. This protective effect of acarbose on age-related behavioral impairments might be related to changes in the insulin system and the levels of BDNF, IGF-1R, and the pre-synaptic proteins Syt1 and Stx1. In conclusion, long-term treatment with acarbose ameliorated the behavioral deficits and biochemical changes in old SAMP8 mice and promoted successful aging. This study provides insight into the potential of acarbose for the treatment of brain aging.
维持胰岛素/胰岛素样生长因子1（IGF-1）信号通路和/或葡萄糖代谢的稳态可能会逆转大脑衰老。在本研究中，我们研究了α-葡萄糖苷酶抑制剂阿卡波糖对与年龄相关的行为和生化变化的影响。将SAMP8小鼠随机分为老年对照组和阿卡波糖治疗组。阿卡波糖组的小鼠在3至9月龄时口服阿卡波糖（20 mg/kg/d，溶于饮用水），同时加入一组新的3月龄小鼠作为年轻对照组。结果显示，老年对照组的感觉运动能力、旷场焦虑、空间和非空间记忆能力下降，血清胰岛素水平降低，海马层中IGF-1受体和突触结合蛋白1（Syt1）水平升高，胰岛素受体、脑源性神经营养因子（BDNF）和 syntaxin 1（Stx1）水平降低。与年龄相关的行为缺陷与血清学和组织化学数据相关。长期阿卡波糖治疗缓解了这些与年龄相关的变化，尤其是在学习和记忆能力方面。阿卡波糖对与年龄相关的行为损伤的这种保护作用可能与胰岛素系统以及BDNF、IGF-1R和突触前蛋白Syt1和Stx1水平的变化有关。总之，长期使用阿卡波糖治疗可改善老年SAMP8小鼠的行为缺陷和生化变化，并促进成功衰老。本研究为阿卡波糖治疗脑衰老的潜力提供了见解。
