丰富环境对脑缺血大鼠突触界面结构修饰和PSD-95基因表达的影响

探讨丰富环境干预对局部脑缺血大鼠突触界面结构修饰和突触后致密物-95 (postsynaptic density-95，PSD-95 ) mRNA表达的影响。栓塞健康雄性Sprague-Dawley大鼠的右侧大脑中动脉，建立脑中动脉栓塞(middle cerebral artery occlusion，MCAO)模型后，分为丰富环境缺血组(IE)、标准环境缺血组(IS)，同时分别设丰富环境假手术组(SE)、标准环境假手术组(SS)。以Morris水迷宫检测大鼠的空间学习记忆能力，应用透射电镜、图像分析和细胞形态计量学技术，观察海马CA1区和额叶皮层突触界面结构变化，采用RT-PCR检测突触后脚手架蛋白PSD-95 mRNA的表达。结果表明：丰富环境干预能有效改善脑缺血导致的空间学习记忆能力下降，并对正常大鼠的空间学习记忆能力也有改善作用。同时，丰富环境干预能抑制局部脑缺血导致的突触数密度减少，该作用对额叶皮层特别明显；丰富环境干预不同程度地逆转脑缺血造成的突触界面参数变化，特别使突触间隙宽度显著减小、PSD厚度明显增加；并有效抑制因脑缺血诱导的PSD-95 mRNA表达下调。以上结果提示，丰富环境改善脑缺血大鼠的空间学习记忆能力可能与其促进缺血区边缘组织突触界面结构修饰，提高PSD-95 mRNA表达有关

The Effects of Enriched Environment on Structural Modification of Synaptic Interface and PSD -95 mRNA of Rats after Transient Focal Cerebral Ischemia

Reports have shown that damage to the adult brain can result in adaptive changes in regions adjacent to or surrounding the site of the principal injury, and that these changes may be modulated by rehabilitation training. An enriched environment has been shown to improve the cognitive, behavioral, and histopathological outcomes following focal cerebral ischemia and head trauma. Morphological changes in areas adjacent to the injury site have been reported following damage to the adult brain. In transient global cerebral ischemia, changes are observed in neuronal and non-neuronal cells in the regions that surround the primary injury site, including dendritic restructuring, reactive changes in glia, reactive synaptogenesis, and enhanced neurogenesis. The purpose of this study was to investigate the effects of an enriched environment on the structural modification of synaptic interface and PSD-95 mRNA of rats following transient focal cerebral ischemia, and elucidate the underlying mechanism. Seventy adult male Sprague-Dawley rats (weight: 250~300 g) were included in this study. A transient ischemic model of rats was established by occluding the right middle cerebral artery (MCAO) with a nylon filament (diameter 0.234 mm). Three days following ischemia or sham surgery, the rats were randomly assigned to the following environmental conditions for 14 days: enriched environment housing (ischemia enriched environment (IE) and sham enriched environment (SE)) or standard environment housing (ischemia standard environment (IS) and sham standard environment (SS)). In order to observe (a) the changes in learning and memory and (b) the ultrastructure of the frontal cortex and hippocampus of the rats following focal cerebral ischemia, the Morris water maze test and transmission electron microscopy, and morphological measurements, respectively, were used in the present study. Simultaneously, the expression of PSD-95 mRNA was measured by RT-PCR. The results of the water maze revealed that although cerebral ischemia significantly damaged the ability of spatial learning and memory, environmental enrichment significantly improved the memory damage induced by cerebral ischemia. Meanwhile, environmental enrichment restrained the reduction of the synaptic density caused by cerebral ischemia, particularly in the frontal cortex. Further, environmental enrichment also reversed the changes in synaptic interface parameters caused by cerebral ischemia at different levels, particularly increasing the thickness of postsynaptic density and decreasing the synaptic cleft width. Furthermore, environmental enrichment significantly up-regulated the expression of PSD-95 mRNA in the ipsilateral cortex and hippocampus of MCAO rats. These results suggest that the enriched environment significantly promoted spatial learning and memory in MCAO rats. The amelioration of structural modification of the synaptic interface and up-regulation of the expression of PSD-95 mRNA were also involved