Neuropathologically distinct prion strains give rise to similar temporal profiles of behavioral deficits
Neuropathologically distinct prion strains give rise to similar temporal profiles of behavioral deficits
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DOI：
10.1016/j.nbd.2004.08.015
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发表时间：
2005-03-01
影响因子：
6.1
通讯作者：
Perry, VH
中科院分区：
文献类型：
--
作者：
Cunningham, C;Deacon, RMJ;Perry, VH
小鼠适应性羊瘙痒病菌株的特点是空泡化和孵育时间，但行为后果还没有得到很好的研究。在这里，我们比较了C57 BL/6 J小鼠中ME 7，79 A，22 L和22 A菌株产生的行为障碍。我们发现，早期损害的穴居，葡萄糖消耗，筑巢和开放的领域活动，和后期运动障碍表现出非常相似的时间序列在ME 7，79 A，和22 L。22 A菌株的长孵育时间产生更晚的损伤。然而，菌株显示出明显的晚期神经病理学差异。所有品系在海马中均显示出明显的小胶质细胞活化和突触丢失，但仅ME 7和79 A显示出显著的CA 1神经元死亡。相反，22 L和22 A显示出显著的小脑浦肯野神经元损失。所有品系均表现出明显的丘脑神经元丢失。这些行为上的相似性加上明显的病理学差异，可以用来识别不同朊病毒株的神经效应的早期功能障碍的关键回路。(C)2004年爱思唯尔公司All rights reserved.
Mouse-adapted scrapie strains have been characterized by vacuolation profiles and incubation times, but the behavioral consequences have not been well studied. Here, we compared behavioral impairments produced by ME7, 79A, 22L, and 22A strains in C57BL/6J mice. We show that early impairments on burrowing, glucose consumption, nesting and open field activity, and late stage motor impairments show a very similar temporal sequence in ME7, 79A, and 22L. The long incubation time of the 22A strain produces much later impairments. However, the strains show clear late stage neuropathological differences. All strains showed clear microglial activation and synaptic loss in the hippocampus, but only ME7 and 79A showed significant CA1 neuronal death. Conversely, 22L and 22A showed significant cerebellar Purkinje neuron loss. All strains showed marked thalamic neuronal loss. These behavioral similarities coupled with clear pathological differences could serve to identify key circuits whose early dysfunction underlies the neurological effects of different prion strains. (C) 2004 Elsevier Inc. All rights reserved.