Multiple sclerosis is an
autoimmune disease characterised by
demyelination in the central nervous system. The
cuprizone-induced
demyelination model is often used in mice to test novel treatments for
multiple sclerosis. However, despite significant
demyelination, behavioural deficits may be subtle or have mixed results depending on the paradigm used. Furthermore, the sex differences within the model are not well understood. In the current study, we have sought to understand the behavioural deficits associated with the
cuprizone-induced
demyelination model in both male and female C57BL/6J mice. Using
Black gold II
stain, we found that
cuprizone administration over 6 weeks caused significant
demyelination in the corpus callosum that was consistent across both sexes.
Cuprizone administration caused increased mechanical sensitivity when measured using an electronic von Frey aesthesiometer, with no sex differences observed. However,
cuprizone administration decreased motor coordination, with more severe deficits seen in males in the horizontal bar and passive wire hang tests. In contrast, female mice showed more severe deficits in the motor skill sequence test.
Cuprizone administration caused more anxiety-like behaviours in males compared to females in the elevated zero maze. Therefore, this study provides a better understanding of the sex differences involved in the behavioural aspects of
cuprizone-induced
demyelination, which could allow for a better translation of results from the laboratory to the clinic.