Striatal pathology underlies prion infection-mediated hyperactivity in mice
Striatal pathology underlies prion infection-mediated hyperactivity in mice
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DOI：
10.4161/pri.4.4.13721
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发表时间：
2010-10-01
期刊：
影响因子：
2.3
通讯作者：
Steele, Andrew D.
中科院分区：
文献类型：
--
作者：
Gunapala, Keith M.;Chang, Daniel;Steele, Andrew D.
尽管Pron病通常是用实验室小鼠来建模的，但Pron菌株的多样性、行为测试和神经病理学评估阻碍了我们对Pron病小鼠模型的集体理解。在这里，我们在C57BL/6J雌性小鼠身上比较了几种常用的鼠型普恩病毒株，在详细的家庭笼子行为检测系统中，并对病理标志物和神经递质系统进行了系统的研究。我们观察到，接种RML或139A普鲁恩的小鼠在家中表现出严重的过度活动表型。小胶质细胞标记物IBA1、星形胶质细胞标记物GFAP和变性染色等病理标记物的详细评估表明，接种RML或139A的小鼠早期纹状体病变，而接种22L普鲁恩的小鼠纹状体早期病理。对包括5-羟色胺、多巴胺、去甲肾上腺素和乙酰胆碱在内的神经调节系统的评估显示，除了背侧纹状体的多巴胺能神经支配略有减少外，控制运动行为的区域的神经元胞体或它们的神经支配几乎没有下降。这些结果表明，背侧纹状体参与了139A和RML蛋白的主要行为表型。此外，他们还提出，对活性的测量可能是诊断小鼠Pron病的一种敏感方式。在神经病理学方面，我们的结果表明，在小鼠模型中，与神经递质标记物相比，病理标记物作为Pron病的标记物更具信息量和敏感性。
Although prion diseases are most commonly modeled using the laboratory mouse, the diversity of prion strains, behavioral testing and neuropathological assessments hamper our collective understanding of mouse models of prion disease. Here we compared several commonly used murine strains of prions in C57BL/6J female mice in a detailed home cage behavior detection system and a systematic study of pathological markers and neurotransmitter systems. We observed that mice inoculated with RML or 139A prions develop a severe hyperactivity phenotype in the home cage. A detailed assessment of pathology markers, such as microglial marker IBA1, astroglial marker GFAP and degeneration staining indicate early striatal pathology in mice inoculated with RML or 139A but not in those inoculated with 22L prions. An assessment of neuromodulatory systems including serotonin, dopamine, noradrenalin and acetylcholine showed surprisingly little decline in neuronal cell bodies or their innervations of regions controlling locomotor behavior, except for a small decrease in dopaminergic innervations of the dorsal striatum. These results implicate the dorsal striatum in mediating the major behavioral phenotype of 139A and RML prions. Further, they suggest that measurements of activity may be a sensitive manner in which to diagnose murine prion disease. With respect to neuropathology, our results indicate that pathological stains as opposed to neurotransmitter markers are much more informative and sensitive as markers of prion disease in mouse models.