Episodic demyelination and subsequent remyelination within the murine central nervous system: changes in axonal calibre.
Exposure of young adult C57BL/6 mice to cuprizone in the diet initiated profound and synchronous demyelination of the corpus callosum, which was virtually complete by 4 weeks of exposure. Interestingly, even in the face of a continued exposure to cuprizone, there was spontaneous remyelination 2 weeks later. This remyelination preferentially involved smaller calibre axons. There was a suggestion of yet another cycle of demyelination (at 10 weeks) and remyelination (at 12 weeks), but by 16 weeks of exposure, the regenerative capacity was exhausted and the animals were near death. The relapsing-remitting pattern suggests this may be a useful model for certain human demyelinating disorders. In contrast to the above chronic model, the corpus callosum from mice exposed to cuprizone for only 6 weeks continued to remyelinate, with 67% of the axons being myelinated or remyelinated at 10 weeks. Interestingly, a significant reduction in the mean value for axonal diameter was observed during acute demyelination. Upon remyelination, however, the axonal calibre distribution returned to near-normal. In contrast, when mice were maintained on a cuprizone diet for 16 weeks, the mean value for axonal diameter was reduced to 60% of normal. These results provide further evidence that the interactions between oligodendrocytes and axons alter axonal calibre.
Mason
J L
JL
Curriculum in Neurobiology and UNC Neuroscience Center, Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Langaman
C
C
Morell
P
P
Suzuki
K
K
Matsushima
G K
GK
D000578:Amidines; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D048429:Cell Size / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology*; D002908:Chronic Disease; D003337:Corpus Callosum / Q000187:drug effects / Q000473:pathology; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D005456:Fluorescent Dyes; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000648:ultrastructure; D012008:Recurrence; D012075:Remission, Spontaneous
D000578:Amidines; D005456:Fluorescent Dyes; C031455:diamidino compound 253-50; D003471:Cuprizone