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Brooke Hawker: Transforming Treats into Tools: Cuprizone-Peanut Butter to Model Demyelination in Mice

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posted on 2024-10-21, 22:38 authored by Brooke HawkerBrooke Hawker, Bronwen ConnorBronwen Connor, Amy McCaughey-Chapman, Ethan Chiddicks

The cuprizone (CPZ) mouse model of demyelination is a well-established model of Multiple sclerosis (MS), inducing central nervous system (CNS) demyelination within 6 weeks. Typically, CPZ is mixed into ground rodent chow, however, its bitter taste reduces food intake, causing severe weight loss and variability in daily CPZ consumption. This leads to inconsistent demyelination, complicating disease comparison between animals. To address this, we propose mixing CPZ into peanut butter (CPZ-PB) as a novel method of CPZ delivery. To assess the use of CPZ-PB to standardize daily dosing and minimise weight loss while maintaining effective demyelination in comparison to CPZ administration through chow (CPZ-Chow). 30 male, C57BL6/J mice were divided into control, CPZ-PB or CPZ-Chow groups (n = 10 per group) and received daily CPZ treatment for 6 weeks. Weight was recorded daily, behavioural testing via the dynamic plantar aesthesiometer (DPA) was conducted at 0, 3 and 6 weeks, and demyelination of the brain and spinal cord was confirmed at 6 weeks via immunohistochemical (IHC) analysis of myelin proteins. CPZ-PB animals consumed a consistent daily dose of CPZ for 6 weeks without experiencing significant weight loss. DPA analysis revealed increased sensitivity to mechanical allodynia with CPZ treatment, which was greater in CPZ-PB animals at 6 weeks (p=0.000305). IHC analysis confirmed comparable levels of demyelination in the brain and spinal cord of both CPZ-PB and CPZ-Chow animals. This study introduces a novel CPZ-intoxication methodology that alleviates welfare concerns and provides a more reliable model for MS research.

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