Selective presynaptic degeneration in the synaptopathy associated with ME7-induced hippocampal pathology
Selective presynaptic degeneration in the synaptopathy associated with ME7-induced hippocampal pathology
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DOI：
10.1016/j.nbd.2009.04.001
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发表时间：
2009-07-01
影响因子：
6.1
通讯作者：
O'Connor, Vincent
中科院分区：
文献类型：
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作者：
Gray, Bryony C.;Siskova, Zuzana;O'Connor, Vincent
海马内注射鼠改良羊瘙痒病（ME7）诱导体内朊病毒病模型。在第8、12和21周将接种ME7脑匀浆的动物与对照组进行比较。数据显示，错误折叠朊病毒（PrPSC）的积累与疾病早期突触前蛋白表达的选择性减少相一致。这种损失是独立的CA3细胞体的数量变化，提供了主要的突触前输入到辐射层。放射层的电子显微镜检查独立地证明了疾病期间突触数量的进行性减少。此外，缺乏完整的突触前特化的突触后特化的数量从12周增加到21周。这表明，突触前区室被选择性地破坏时，先前报道的第一个行为缺陷，在这个模型中观察到。这种突触病理或“突触病”可能代表这种和其他蛋白质错误折叠诱导的神经变性疾病中最早的神经元功能障碍。(C)2009 Elsevier Inc. All rights reserved.
Intrahippocampal injection of the murine modified scrapie (ME7) induces a model of prion disease in vivo. Animals inoculated with ME7 brain homogenate were compared to controls at 8,12 and 21 weeks. The data show that the accumulation of misfolded prion (PrPSC) coincided with selective reduction in presynaptic protein expression early in disease. This loss is independent of a change in the number of cell bodies in CA3 that provide the major presynaptic input to the stratum radiatum. Electron microscopy of the stratum radiatum independently evidenced a progressive decrease in the number of synapses during disease. Further, the number of postsynaptic specializations lacking an intact presynaptic specialization increased from 12 to 21 weeks. This suggests that the presynaptic compartment is selectively disrupted when the previously reported first behavioural deficits are observed in this model. This synaptic pathology or "synaptopathy" may represent the earliest neuronal dysfunction in this and other protein misfolding induced neurodegenerative diseases. (C) 2009 Elsevier Inc. All rights reserved.