Defining milestones for the study of remyelination using the cuprizone mouse model: How early is early?

Background: Cuprizone (CPZ) is a copper chelator used to produce a reversible oligodendrocytopathy in animals, which has some similarities to the pathology found in human multiple sclerosis (MS). This model is attractive to study remyelination. Aims: To demonstrate that a two-week period after cessation of CPZ exposure is sufficient to establish changes compatible with remyelination, without accompanying behavior or brain magnetic resonance imaging (MRI) disturbances. Methods: Two groups of male C57BL/6 mice were fed an oral solution of CPZ (0.2%) for 5 weeks (W5); half of the animals were kept under the vehicle for another 2 weeks (W7). After 5 and 7 weeks, animals were subjected to a battery of behavioural tests and 18 animals to brain MRI. Animals' cerebellar samples were studied for gene expression and/or protein levels of GFAP, myelin proteolipid protein (PLP), TNF-alpha and IL-1 beta. Results: No differences were observed between CPZ-exposed and control animals, regarding behavior and MRI, both at W5 and W7. However, myelin PLP levels decreased in CPZ (W5) treated animals, and these changes reverted at W7. GFAP levels varied in the opposite direction. Conclusions: Observed changes validate the use of W5 and W7 temporal moments for the study of demyelination and early remyelination in this model.

Automated summary

The study demonstrates that a two-week period after cessation of Cuprizone exposure is sufficient to establish changes compatible with remyelination. This provides a time window for studying demyelination and early remyelination.