Evaluation of the Behavioral and Histopathological Outcomes of Two Cuprizone Administration Routes in a Mouse Model...

The cuprizone (CPZ) model has been used to study de- and re-myelination in mice; Previous studies have used different routes for CPZ intoxication, but the results were highly variable.

Here, we compared demyelination induced by the administration of 0.3% CPZ mixed with ground rodent chow and a 400 mg/kg CPZ suspension in carboxymethyl cellulose (CMC) via oral gavage in SWR/J mice. The mice were assigned into a control group, a CPZ diet group, and an oral CPZ groups (n = 6 mice/group). Rotarod, hanging wire, and open field tests were performed to evaluate locomotor activity. Histological analyses were conducted on the corpus callosum (CC) of the brain to determine myelin loss and on the liver to assess the toxicity of CPZ.

The administration of CPZ with ground rodent chow significantly reduced body weight gains, grip strength, and motor coordination performance during the 5-week demyelination period. In contrast, all analyzed parameters were less different in mice receiving CPZ via oral gavage. However, both CPZ routes significantly reduced myelin content in the CC. Additionally, the oral administration of CPZ had strong effects on liver toxicity compared to that of CPZ diet feeding. This study showed that both routes of CPZ intoxication could induce reproducible and consistent demyelination changes within the CC of the mouse brain, with the CPZ diet being more effective based on all analytical parameters and having fewer toxic effects on the liver compared with oral CPZ.

In conclusion, the resultsassist in the selection of a suitable multiple sclerosis (MS) model for investigating disease mechanisms and therapies.