title: Cuprizone treatment induces demyelination and astrocytosis in the mouse hippocampus.
abstract: Memory impairment is outstanding within the spectrum of cognitive deficits in multiple sclerosis (MS) patients. Demyelination has been reported in the hippocampus formation of MS patients. The degree of hippocampus lesions in MS strongly correlates with progression of cognitive dysfunction. Because no appropriate animal model for the study of hippocampus demyelination has been established, we used the cuprizone mouse model to investigated demyelination in young adult and aged mice. The myelin status was analyzed by classical histological staining, immunocytochemistry for proteolipoprotein, and electron microscopy. Oligodendrocyte, astroglial, and microglia markers were studied. Cuprizone intoxication induced an almost complete demyelination of distinct hippocampus subregions to a similar extent in young adult and aged male mice. Demyelination was pronounced in a subset of white and gray matter areas, i.e., the stratum lacunosum moleculare containing the perforant path, medial alveus, stratum pyramidale in the cornu ammonis 2/3 region, and hilus region. Besides demyelination, affected areas displayed hypertrophic and hyperplastic astrocytosis. No significant effect on microglia invasion was detected at any investigated time point (0, 3, 5, and 7 weeks). We conclude that cuprizone-induced demyelination provides an adequate animal model to investigate appropriate therapy strategies for the prevention of hippocampus demyelination.
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
authors.forename: Akvile
authors.initials: A
authors.lastname: Norkute
authors.forename: Andrea
authors.initials: A
authors.lastname: Hieble
authors.forename: Alena
authors.initials: A
authors.lastname: Braun
authors.forename: Sonja
authors.initials: S
authors.lastname: Johann
authors.forename: Tim
authors.initials: T
authors.lastname: Clarner
authors.forename: Werner
authors.initials: W
authors.lastname: Baumgartner
authors.forename: Cordian
authors.initials: C
authors.lastname: Beyer
authors.forename: Markus
authors.initials: M
authors.lastname: Kipp
mesh_terms: D000375:Aging; D000818:Animals; D001253:Astrocytes / Q000473:pathology; D003471:Cuprizone / Q000494:pharmacology*; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology; D006624:Hippocampus / Q000473:pathology* / Q000648:ultrastructure; D007150:Immunohistochemistry; D007211:Indoles; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000473:pathology; D008854:Microscopy, Electron; D009103:Multiple Sclerosis; D009186:Myelin Sheath / Q000648:ultrastructure; D009836:Oligodendroglia / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007211:Indoles; C018588:Luxol Fast Blue MBS; D003471:Cuprizone