Environmental Enrichment Induces Synaptic Structural Modification After Transient Focal Cerebral Ischemia in Rats
Environmental Enrichment Induces Synaptic Structural Modification After Transient Focal Cerebral Ischemia in Rats
复制标题
环境丰富在大鼠短暂性局灶性脑缺血后诱导突触结构改变
DOI：
10.3181/0804-rm-128
复制
发表时间：
2009-03-01
影响因子：
3.2
通讯作者：
Ruan, Qin
中科院分区：
文献类型：
--
作者：
Xu, Xiaohong;Ye, Lingjing;Ruan, Qin
环境富集（EE），其中动物暴露于一个复杂的新环境，已被证明可以诱导突触可塑性在完整和受伤的动物。本研究旨在探讨EE对短暂性局灶性脑缺血大鼠空间记忆和突触连接结构改变的影响。成年雄性Sprague-Dawley大鼠进行右侧大脑中动脉闭塞（MCAO）40分钟和再灌注。在MCAO或假手术后第3天，将大鼠随机分配到富集或标准环境饲养区14天。然后通过Morris水迷宫测试空间记忆。顶叶皮层和海马CA 1区的电子显微镜和体视学技术被用来评估突触连接的可塑性。MCAO后EE改善了空间记忆，缩短了逃逸长度，增加了平台位置处的交叉频率，并增加了平台先前所在象限的时间百分比。突触超微结构分析表明，MCAO后EE增加了顶叶皮层的数字突触密度，并引起了突触连接的结构变化，其中顶叶皮层和海马的突触裂隙宽度减小，突触后密度（PSD）厚度增加，伴随着空间记忆任务的改善。使用Western印迹分析，我们确定了谷氨酸受体NMDAR 1和PSD-95的表达，PSD-95是PSD-95家族中最具特征的蛋白质成员，其在兴奋性突触的PSD中大量表达。结果表明，EE组MCAO大鼠脑组织中NMDAR 1含量无明显变化，但磷酸化NMDAR 1水平较标准环境组明显升高。EE还能抑制MCAO引起的顶叶皮层和海马PSD-95表达的降低。这些数据表明，改善脑缺血大鼠的空间记忆EE与突触连接在几个脑区的结构修饰。实验生物医学234：296-305，2009
Environmental enrichment (EE), where animals are exposed to a complex novel environment, has been shown to induce synaptic plasticity in both intact and injured animals. The purpose of this study was to investigate the effects of EE on spatial memory and structural modifications of synaptic junctions in rats following transient focal cerebral ischemia. Adult male Sprague-Dawley rats underwent right middle cerebral artery occlusion (MCAO) for 40 min and reperfusion. On day 3 after MCAO or sham surgery, rats were randomly assigned for 14 days to enriched or standard environmental housing. Spatial memory was then tested by the Morris water maze. Parietal cortex and the CA1 region of hippocampus were processed for electron microscopy and stereological techniques were used to evaluate plasticity of synaptic junctions. EE after MCAO improved spatial memory, with shortened escape length, increased frequency of crossings at the location of the platform, and increased percentage of time spent in the quadrant where the platform was previously located. Synaptic ultrastructural analysis showed that EE after MCAO increased numeric synaptic density in parietal cortex, and induced structural changes in synaptic junctions, with a decreased width of synaptic clefts and increased thickness of postsynaptic densities (PSD) in parietal cortex and hippocampus, accompanying improved performance on the spatial memory task. Using Western blot analysis, we determined the expression of glutamate receptor NMDAR1, and PSD-95, the best characterized protein member of the PSD-95 family, that was abundantly expressed in the PSD of excitatory synapses. The results showed that the content of NMDAR1 was not altered in MCAO rats of EE; however, the phosphorylated NMDAR1 increased significantly when compared with the standard environment housing MCAO rats. In addition, EE inhibited the impaired expression of PSD-95 induced by MCAO in parietal cortex and hippocampus. These data suggest that improved spatial memory of cerebral ischemic rats by EE is associated with structural modifications of synaptic junctions in several brain regions. Exp Biol Med 234:296-305, 2009