title: Anatomical Distribution of Cuprizone-Induced Lesions in C57BL6 Mice.
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.
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, 52074, Aachen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Goldberg
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, 52074, Aachen, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Clarner
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, 52074, Aachen, Germany.
authors.forename: Cordian
authors.initials: C
authors.lastname: Beyer
authors.affiliation: Department of Anatomy II, Ludwig-Maximilians-University of Munich, 80336, Munich, Germany. mkipp@ukaachen.de.|Lehrstuhl II-Neuroanatomie, Anatomische Anstalt, Pettenkoferstr. 11, 80336, München, Germany. mkipp@ukaachen.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Kipp
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D003337:Corpus Callosum / Q000473:pathology; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D066128:Gray Matter / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity*; D009186:Myelin Sheath / Q000473:pathology*; D066127:White Matter / Q000473:pathology*
chemical_list: D008996:Monoamine Oxidase Inhibitors; D003471:Cuprizone
keywords: Axonal damage; Cuprizone; Demyelination; Gray matter; Microglia; Neurodegeneration; White matter