Dendritic and synaptic alterations of hippocampal pyramidal neurones in scrapie-infected mice
Dendritic and synaptic alterations of hippocampal pyramidal neurones in scrapie-infected mice
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DOI：
10.1046/j.1365-2990.2000.026002143.x
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发表时间：
2000-04-01
影响因子：
5
通讯作者：
Fraser, JR
中科院分区：
文献类型：
--
作者：
Belichenko, PV;Brown, D;Fraser, JR
神经元损伤以及最终的丧失可能是传染性海绵状脑病（TSE）临床症状的基础。尽管神经元死亡似乎是通过细胞凋亡发生的，但在TSE中这种细胞死亡形式的触发因素尚不清楚。利用两种不同的小鼠痒病模型，通过显微注射荧光染料对海马锥体细胞进行研究，并利用p38免疫反应性（p38 - IR）研究突触完整性，两者均使用共聚焦激光扫描显微镜进行观察。在感染ME7或87V痒病的小鼠海马中，发现树突内肿胀和树突棘丧失与空泡和朊病毒蛋白病变区域共定位。同时在ME7痒病小鼠的海马中发现p38 - IR显著降低。这些结果表明，突触前和突触后位点都因痒病感染而改变；这将破坏神经元回路，并可能引发细胞凋亡，导致临床TSE病例中出现的神经紊乱。
Neurone damage and eventual loss may underlie the clinical signs of disease in the transmissible spongiform encephalopathies (TSEs). Although neurone death appears to be through apoptosis, the trigger for this form of cell death in the TSEs is not known. Using two different murine scrapie models, hippocampal pyramidal cells were studied through microinjection of fluorescent dye, and synaptic integrity, using p38-immunoreactivity (p38-IR), both visualized using confocal laser scanning microscopy. Intradendritic distensions and dendritic spine loss were found to co-localize to areas of vacuolar and prion protein pathology in the hippocampus of mice infected with ME7 or 87 V scrapie. A significant reduction in p38-IR was found concomitantly in the hippocampus in ME7 scrapie mice. These results indicate that both pre- and post-synaptic sites are altered by scrapie infection; this would disrupt neuronal circuitry and may initiate apoptotic cell death, giving rise to the neurological disturbances manifested in clinical TSE cases.