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 (3): 462-469.doi: 10.4103/1673-5374.245470

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

富集环境增强永久性脑缺血性小鼠的突触可塑性和促进认知功能恢复

  

  • 出版日期:2019-03-15 发布日期:2019-03-15
  • 基金资助:

    国家自然科学基金(81672242)；上海市卫生与计划生育薄弱学科重点建设项目(2015ZB0401)

An enriched environment promotes synaptic plasticity and cognitive recovery after permanent middle cerebral artery occlusion in mice

Chuan-Jie Wang, Yi Wu , Qun Zhang, Ke-Wei Yu, Yu-Yang Wang   

  1. Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
  • Online:2019-03-15 Published:2019-03-15
  • Contact: Yi Wu, MD, wuyi@fudan.edu.cn.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81672242 (to YW) and the Key Construction Projects of Shanghai Health and Family Planning on Weak Discipline, China, No. 2015ZB0401 (to YW).

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摘要：

缺血性卒中后可以诱导启动大脑的内源性修复程序，该程序被认为与促进内源性神经元的可塑性过程有关。为了探索研究丰富环境对久性脑缺血性小鼠空间学习记忆及突出重塑中的作用，实验将成年雄性C57BL/6小鼠制备为永久性左侧大脑中动脉闭塞模型。术后3 d，模型小鼠随机分为标准饲养组及丰富环境组，标准饲养组动物为正常饲养标准饲养，丰富环境组在标准饲养的基础上，在鼠笼内加入各种玩具。术后28 d，使用Morris水迷宫试验来测试小鼠的空间学习及记忆能力，使用Western blot法测量小鼠海马区轴突末端蛋白标记物生长相关蛋白43，突触前膜蛋白标记物突触素，突触后膜蛋白标记物突触后密度蛋白95的蛋白表达，以及使用电镜技术来评估小鼠海马区突触数量的变化。结果显示：(1)在水迷宫实验测试中，丰富环境组小鼠较标准饲养组小鼠能更快的学习找到隐藏在水中的平台，在目标象限中游动的距离和时间以及穿过原平台的次数也较标准饲养组多；(2)丰富环境组较标准饲养组小鼠海马区生长相关蛋白43、突触素及突触后密度蛋白95的蛋白表达明显提高；(3)通过电镜观察发现，丰富环境提高了小鼠海马CA1区突触的数量；(4)上述数据表明，丰富环境可以改善永久性脑缺血所致的空间学习及记忆功能损害，该作用可能是通过突触机制介导的。

orcid: 0000-0003-4854-9898(Yi Wu)

关键词: 丰富环境, 缺血性卒中, 认知功能恢复, 大脑重塑与重组, 突触重塑, 电镜, GAP-43, SYN, PSD-95, pMCAO, 神经再生

Abstract:

Cerebral ischemia activates an endogenous repair program that induces plastic changes in neurons. In this study, we investigated the effects of environmental enrichment on spatial learning and memory as well as on synaptic remodeling in a mouse model of chronic cerebral ischemia, produced by subjecting adult male C57BL/6 mice to permanent left middle cerebral artery occlusion. Three days post¬operatively, mice were randomly assigned to the environmental enrichment and standard housing groups. Mice in the standard housing group were housed and fed a standard diet. Mice in the environmental enrichment group were housed in a cage with various toys and fed a standard diet. Then, 28 days postoperatively, spatial learning and memory were tested using the Morris water maze. The expression levels of growth-associated protein 43, synaptophysin and postsynaptic density protein 95 in the hippocampus were analyzed by western blot assay. The number of synapses was evaluated by electron microscopy. In the water maze test, mice in the environmental enrichment group had a shorter escape latency, traveled markedly longer distances, spent more time in the correct quadrant (northeast zone), and had a higher frequency of crossings compared with the standard housing group. The expression levels of growth-associated protein 43, synaptophysin and postsynaptic density protein 95 were substantially upregulated in the hippocampus in the environmental enrichment group compared with the standard housing group. Furthermore, electron microscopy revealed that environmental enrichment increased the number of synapses in the hippocampal CA1 region. Collectively, these findings suggest that environmental enrichment ameliorates the spatial learning and memory impairment induced by permanent middle cerebral artery occlusion. Environmental enrichment in mice with cerebral ischemia likely promotes cognitive recovery by inducing plastic changes in synapses.

Key words: nerve regeneration, environmental enrichment, cerebral ischemia, cognitive recovery, brain plasticity and reorganization, synaptic plasticity, electron microscopy, growth-associated protein 43, synaptophysin, postsynaptic density protein 95, permanent middle cerebral artery occlusion, neural regeneration