title: Remyelination After Cuprizone-Induced Demyelination Is Accelerated in Juvenile Mice.
abstract: Remyelination capacity decreases with age in adult mice, but data comparing remyelination capacity after toxic demyelination in developing mice versus adult mice are not available. We treated 3-week-old and adult C57BL/6 mice with cuprizone for 1 to 5 weeks and studied demyelination/remyelination and cellular reactions in the corpus callosum and motor cortex by histology, immunohistochemistry, and electron microscopy. We compared results between the 2 treated groups and age-matched controls. In juvenile mice, significant demyelination was detectable in the corpus callosum on Week 2 and in the motor cortex on Week 5. Oligodendrocyte loss, microglial activation, and acute axonal damage peaked on Week 2. Increased numbers of oligodendrocyte precursor cells were evident on Week 1, and remyelination was detectable on Week 3. Juvenile mice showed more rapid demyelination than adult mice, which may be related to greater vulnerability of oligodendrocytes, lower myelin content, or dose-dependent cuprizone effects. Earlier activation of microglia and proliferation of oligodendrocyte precursor cells probably contributed to accelerated remyelination and less pronounced axonal damage. Our data indicate that oligodendroglial regeneration and remyelination are enhanced in the maturing rodent brain compared with the young-adult rodent brain.
authors.affiliation: From the Department of Neuropathology, University Medical Center, Georg August University, Göttingen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Pfeifenbring
authors.forename: Stefan
authors.initials: S
authors.lastname: Nessler
authors.forename: Christiane
authors.initials: C
authors.lastname: Wegner
authors.forename: Christine
authors.initials: C
authors.lastname: Stadelmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000473:pathology*; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity; D009416:Nerve Regeneration / Q000502:physiology*; D009836:Oligodendroglia / Q000473:pathology
chemical_list: D008996:Monoamine Oxidase Inhibitors; D003471:Cuprizone