Early increase and late decrease of purkinje cell dendritic spine density in prion-infected organotypic mouse cerebellar cultures.
Early increase and late decrease of purkinje cell dendritic spine density in prion-infected organotypic mouse cerebellar cultures.
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DOI：
10.1371/journal.pone.0081776
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sim VL
中科院分区：
文献类型：
--
作者：
Campeau JL;Wu G;Bell JR;Rasmussen J;Sim VL
Prion病是一种感染性神经退行性疾病，与蛋白酶抗性的Prion蛋白积聚、神经元丢失、海绵状改变和星形胶质细胞增生有关。在小鼠模型中，树突棘的丢失是体内观察到的最早的病理变化之一，发生在第一次在大脑中检测到具有蛋白酶抗性的Prion蛋白的4-5周后。虽然已经有了Pron感染的细胞培养模型，但大多数模型都不能概括体内的神经病理学。只有最近发展起来的Prion器官型切片培养方法被报道经历了神经元的丢失和Prion病理的某些方面的发展，即小空泡变性和管室小体。考虑到在这个培养系统中Prion的快速复制，21天就可以检测到抗蛋白酶的Prion蛋白，我们调查了在Prion病中看到的树突棘丢失和树突状细胞形态改变是否也可能在该培养系统的生命周期内发展。事实上，在感染RML Pron株的tga20小鼠小脑切片培养物中首次检测到抗蛋白酶的Prion蛋白六周后，我们发现感染的培养物中浦肯野细胞树突棘显著丢失，树突状细胞形态改变，类似于体内看到的情况。此外，我们发现在感染期间浦肯野细胞树突棘密度有短暂的但统计上显著的增加，这是在培养中首次检测到具有蛋白酶抗性的普恩蛋白的时候。我们的发现支持使用这种切片培养系统作为一种概括Pron病病理的系统，并可能有助于研究Prion病的早期发病机制。
Prion diseases are infectious neurodegenerative diseases associated with the accumulation of protease-resistant prion protein, neuronal loss, spongiform change and astrogliosis. In the mouse model, the loss of dendritic spines is one of the earliest pathological changes observed in vivo, occurring 4–5 weeks after the first detection of protease-resistant prion protein in the brain. While there are cell culture models of prion infection, most do not recapitulate the neuropathology seen in vivo. Only the recently developed prion organotypic slice culture assay has been reported to undergo neuronal loss and the development of some aspects of prion pathology, namely small vacuolar degeneration and tubulovesicular bodies. Given the rapid replication of prions in this system, with protease-resistant prion protein detectable by 21 days, we investigated whether the dendritic spine loss and altered dendritic morphology seen in prion disease might also develop within the lifetime of this culture system. Indeed, six weeks after first detection of protease-resistant prion protein in tga20 mouse cerebellar slice cultures infected with RML prion strain, we found a statistically significant loss of Purkinje cell dendritic spines and altered dendritic morphology in infected cultures, analogous to that seen in vivo. In addition, we found a transient but statistically significant increase in Purkinje cell dendritic spine density during infection, at the time when protease-resistant prion protein was first detectable in culture. Our findings support the use of this slice culture system as one which recapitulates prion disease pathology and one which may facilitate study of the earliest stages of prion disease pathogenesis.
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影响因子：
64.8
作者：
Moreno, Julie A.;Radford, Helois;Peretti, Diego;Steinert, Joern R.;Verity, Nicholas;Martin, Maria Guerra;Halliday, Mark;Morgan, Jason;Dinsdale, David;Ortori, Catherine A.;Barrett, David A.;Tsaytler, Pavel;Bertolotti, Anne;Willis, Anne E.;Bushell, Martin;Mallucci, Giovanna R.
通讯作者：
Mallucci, Giovanna R.
DOI：
10.1046/j.1365-2990.2000.026002143.x
发表时间：
2000-04-01
影响因子：
5
作者：
Belichenko, PV;Brown, D;Fraser, JR
通讯作者：
Fraser, JR
影响因子：
6.7
作者：
Falsig, Jeppe;Sonati, Tiziana;Aguzzi, Adriano
通讯作者：
Aguzzi, Adriano
影响因子：
5.3
作者：
Fuhrmann, Martin;Mitteregger, Gerda;Herms, Jochen
通讯作者：
Herms, Jochen
影响因子：
6.1
作者：
Johnston, AR;Fraser, JR;MacLeod, N
通讯作者：
MacLeod, N