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Cuprizone treatment induces demyelination and astrocytosis in the mouse hippocampus
Author(s) -
Norkute Akvile,
Hieble Andrea,
Braun Alena,
Johann Sonja,
Clarner Tim,
Baumgartner Werner,
Beyer Cordian,
Kipp Markus
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21946
Subject(s) - astrocytosis , hippocampus , microglia , hippocampal formation , neuroscience , pathology , multiple sclerosis , myelin , white matter , dentate gyrus , perforant path , psychology , medicine , central nervous system , magnetic resonance imaging , immunology , inflammation , radiology
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. © 2008 Wiley‐Liss, Inc.