中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (4): 649-657.doi: 10.4103/1673-5374.245477

• 原著:退行性病与再生 • 上一篇    下一篇

睾酮对阿尔茨海默病模型大鼠认知功能障碍的保护机制

  

  • 出版日期:2019-04-15 发布日期:2019-04-15
  • 基金资助:

    内蒙古自治区自然科学基金(2017LH0301，2016MS08108)；中国内蒙古自治区科技规划项目(201602069)；包头医学院博士科研基金(BSJJ201606)；包头医学院“登峰工程”科学研究基金(BYJJ-DF 201703)

Protective mechanism of testosterone on cognitive impairment in a rat model of Alzheimer’s disease

Xu-Sheng Yan 1 , Zhan-Jun Yang 1 , Jian-Xin Jia 1 , Wei Song 1 , Xin Fang 1 , Zhi-Ping Cai 1 , Dong-Sheng Huo 1 , He Wang 2   

  1. 1 Department of Human Anatomy, Baotou Medical College, Baotou, Inner Mongolia Autonomous Region, China
    2 School of Health Sciences, University of Newcastle, Newcastle, Australia
  • Online:2019-04-15 Published:2019-04-15
  • Contact: Jian-Xin Jia, PhD, jiajianxindx@163.com.
  • Supported by:

    This study was supported by the Natural Science Foundation of Inner Mongolia Autonomous Region of China, No. 2017LH0301 (to JXJ), 2016MS08108 (to ZJY); the Science and Technology Planning Project of Inner Mongolia Autonomous Region of China, No. 201602069 (to ZJY); the PhD Scientific Research Fund of Baotou Medical College of China, No. BSJJ201606 (to JXJ); the “Dengfeng Project” Scientific Research Fund of Baotou Medical College of China, No. BYJJ-DF 201703 (to JXJ).

PDF

439

摘要：

阿尔茨海默病相关学习认知功能障碍与突触可塑性下降密切相关，而氧化应激损伤可以导致突触可塑性下降。研究表明睾酮在改善学习和记忆方面发挥重要的作用，但其潜在的神经保护机制仍不清楚。为此，实验拟探讨皮下注射0.75 mg睾酮对双侧脑室注射β-淀粉样蛋白1-42寡聚体(Aβ1-42)诱导的雄性阿尔茨海默病模型大鼠认知功能障碍的保护机制。可将结果为：(1)Morris水迷宫实验显示：睾酮治疗显著减少阿尔茨海默病模型大鼠逃避潜伏期和寻找平台的游泳距离，显著提高阿尔茨海默病模型大鼠目标象限时间百分比和穿越平台次数，而雄激素受体拮抗剂氟他胺明显地阻断了睾酮对阿尔茨海默病模型大鼠认知障碍的保护作用；(2)以尼氏染色、免疫组织化学染色、Western blot及ELISA检测显示：睾酮治疗的阿尔茨海默病模型大鼠海马CA1区完整锥体细胞数量、树突棘密度、海马突触后膜致密物95免疫反应及蛋白表达、超氧化物歧化酶和谷胱甘肽过氧化物酶的活性均显著增加，丙二醛含量降低，而氟他胺几乎抑制了睾酮对上述指标的作用；(3)上述数据显示，睾酮通过介导雄激素受体来清除自由基，进而增强突触可塑性，实现对阿尔茨海默病认知功能障碍的保护作用。

orcid: 0000-0001-8578-5115(Jian-Xin Jia)

关键词: 阿尔茨海默病, 睾酮, 认知功能障碍, 突触可塑性, 自由基, Morris水迷宫, 雄激素受体, 氟他胺, 突触后膜致密物95, &beta, -淀粉样蛋白1-42, 神经退行性变, 神经再生

Abstract:

Cognitive dysfunction in Alzheimer’s disease is strongly associated with a reduction in synaptic plasticity, which may be induced by oxida-tive stress. Testosterone is beneficial in learning and memory, although the underlying protective mechanism of testosterone on cognitive performance remains unclear. This study explored the protective mechanism of a subcutaneous injection of 0.75 mg testosterone on cognitive dysfunction induced by bilateral injections of amyloid beta 1–42 oligomers into the lateral ventricles of male rats. Morris water maze test results demonstrated that testosterone treatment remarkably reduced escape latency and path length in Alzheimer’s disease rat models. During probe trials, testosterone administration significantly elevated the percentage of time spent in the target quadrant and the number of platform crossings. However, flutamide, an androgen receptor antagonist, inhibited the protective effect of testosterone on cognitive performance in Alzheimer’s disease rat models. Nissl staining, immunohistochemistry, western blot assay, and enzyme-linked immunosorbent assay results showed that the number of intact hippocampal pyramidal cells, the dendritic spine density in the hippocam¬pal CA1 region, the immune response and expression level of postsynaptic density protein 95 in the hippocampus, and the activities of superoxide dismutase and glutathione peroxidase were increased with testosterone treatment. In contrast, testosterone treatment reduced malondialdehyde levels. Flutamide inhibited the effects of testosterone on all of these indicators. Our data showed that the protective effect of testosterone on cognitive dysfunction in Alzheimer’s disease is mediated via androgen receptors to scavenge free radicals, thereby en¬hancing synaptic plasticity.

Key words: nerve regeneration, Alzheimer’s disease, testosterone, cognitive dysfunction, synaptic plasticity, free radicals, Morris water maze, androgen receptor, flutamide, postsynaptic density protein 95, amyloid beta 1–42, neurodegenerative change, neural regeneration