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Anatomical Distribution of Cuprizone-Induced Lesions in C57BL6 Mice

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Abstract

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.

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Acknowledgments

We would like to thank Helga Helten and Petra Ibold for excellent technical assistance. This study was supported by a grant from ProMyelo–SFZ (MK) and by a financial support of Novartis Pharma GmbH.

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Authors and Affiliations

  1. Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, 52074, Aachen, Germany

    Johannes Goldberg, Tim Clarner & Cordian Beyer

  2. Department of Anatomy II, Ludwig-Maximilians-University of Munich, 80336, Munich, Germany

    Markus Kipp

  3. Lehrstuhl II–Neuroanatomie, Anatomische Anstalt, Pettenkoferstr. 11, 80336, München, Germany

    Markus Kipp

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  1. Johannes Goldberg
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  2. Tim Clarner
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  4. Markus Kipp
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Correspondence to Markus Kipp.

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Goldberg, J., Clarner, T., Beyer, C. et al. Anatomical Distribution of Cuprizone-Induced Lesions in C57BL6 Mice. J Mol Neurosci 57, 166–175 (2015). https://doi.org/10.1007/s12031-015-0595-5

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  • DOI: https://doi.org/10.1007/s12031-015-0595-5

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