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

• Published in: Multiple sclerosis and related disorders 2022-07, Vol.63, p.103886-103886, Article 103886
• Main Authors: Palavra, Filipe, Viana, Sofia D., Henriques, Sara, Dinis, João, Martins, João, Madeira, Maria H., Santiago, Raquel, Petrella, Lorena, Sereno, José, Castelo-Branco, Miguel, Pereira, Frederico C., Almeida, Luís, Ambrósio, António F., Reis, Flávio
• Format: Article
• Language: English
• Subjects: Cuprizone; Demyelination; Multiple sclerosis; Remyelination
• ISSN: 2211-0348; 2211-0356
• DOI: 10.1016/j.msard.2022.103886

•The animal model of cuprizone (CPZ)-induced demyelination is interesting for studying the mechanisms involved in remyelination.•Two weeks after cessation of a 5-week period of CPZ exposure is sufficient to establish changes compatible with remyelination, in biochemical terms, without accompanying behavior or brain magnetic resonance imaging disturbances.•This study validates the use of week 5 and week 7 temporal moments for the study of demyelination and early remyelination in this model.•Deepening the knowledge related to this early remyelination may be useful to identify new therapeutic targets that could translate into the development of potential new remyelination-promoting drugs. 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. 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. 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-α and IL-1β. 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. Observed changes validate the use of W5 and W7 temporal moments for the study of demyelination and early remyelination in this model.