Anatomical Distribution of Cuprizone-Induced Lesions in C57BL6 Mice
Anatomical Distribution of Cuprizone-Induced Lesions in C57BL6 Mice
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DOI：
10.1007/s12031-015-0595-5
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发表时间：
2015-10-01
影响因子：
3.1
通讯作者：
Kipp, Markus
中科院分区：
文献类型：
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作者：
Goldberg, Johannes;Clarner, Tim;Kipp, Markus
虽然多发性硬化症(MS)被认为是一种白质疾病，但多发性硬化症的损害经常发生在大脑的灰质部分。灰质脱髓鞘和萎缩是在疾病的早期阶段发现的，越来越多的证据表明灰质病理与运动障碍和认知障碍的各种指标呈正相关。经典的脑白质脱髓鞘模型被认为是Cuprizone模型。然而，最近的证据表明，不同的灰质区域也会受到影响。在这项研究中，我们解决了前脑白质和灰质区域的易损性在铜试剂盒模型中。在这个模型中，作为大脑半球间白质束的穹隆体白质束受到影响，而其他白质束，如乳房-丘脑束、穹隆柱、终纹、视束或海马伞，在5周铜中毒后不会出现明显的脱髓鞘。相反，灰质脱髓鞘在这个模型中很普遍。此外，脆弱的白质束表现为广泛的急性轴索损伤。这些结果强调了铜试剂模型在研究MS相关灰质病理和神经退行性变方面的相关性。
Although multiple sclerosis (MS) has been considered a white matter disease, MS lesions occur frequently in the gray matter parts of the brain. Gray matter demyelination and atrophy are found during earliest disease stages, and a growing body of evidence demonstrates a positive correlation between gray matter pathology and various measures of motor disability and cognitive impairment. The cuprizone model is classically regarded as white matter demyelination model. However, recent evidence suggests that different gray matter areas are also affected. In this study, we address the vulnerability of white and gray matter forebrain regions in the cuprizone model. While the corpus callosum as interhemispheric white matter tract is affected in this model, other white matter tracts such as the mammillo-thalamic tract, the columns of the fornix, the stria terminalis, the optic tract, or hippocampal fimbria do not present overt demyelination after 5-week cuprizone intoxication. In contrast, gray matter demyelination is widespread in this model. Furthermore, vulnerable white matter tracts display extensive acute axonal damage. These results highlight the relevance of the cuprizone model to study MS-related gray matter pathology and neurodegeneration.