Sex Differences in the Behavioural Aspects of the Cuprizone-Induced Demyelination Model in Mice

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...

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Bibliographic Details
Published in:Brain sciences 2022-12, Vol.12 (12), p.1687
Main Authors: Paton, Kelly F, Hong, Sheein, Biggerstaff, Andrew, Kivell, Bronwyn M
Format: Article
Language:English
Subjects:
Anxiety
Autoimmune diseases
Central nervous system
Corpus callosum
Cuprizone
Demyelination
Females
Gender differences
Immune system
Intoxication
Males
Motor ability
motor coordination
Motor skill
Multiple sclerosis
Sex differences
Software
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Summary: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.
ISSN:2076-3425
2076-3425
DOI:10.3390/brainsci12121687