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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Main Authors: Kelly F. Paton, Sheein Hong, Andrew Biggerstaff, Bronwyn M. Kivell
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Brain Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3425/12/12/1687
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author Kelly F. Paton
Sheein Hong
Andrew Biggerstaff
Bronwyn M. Kivell
author_facet Kelly F. Paton
Sheein Hong
Andrew Biggerstaff
Bronwyn M. Kivell
author_sort Kelly F. Paton
collection DOAJ
description 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.
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spelling doaj.art-bd9ea3cf9e564ff094ec2e868e086c142023-11-24T13:39:59ZengMDPI AGBrain Sciences2076-34252022-12-011212168710.3390/brainsci12121687Sex Differences in the Behavioural Aspects of the Cuprizone-Induced Demyelination Model in MiceKelly F. Paton0Sheein Hong1Andrew Biggerstaff2Bronwyn M. Kivell3Centre for Biodiscovery, School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New ZealandCentre for Biodiscovery, School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New ZealandCentre for Biodiscovery, School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New ZealandCentre for Biodiscovery, School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New ZealandMultiple 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.https://www.mdpi.com/2076-3425/12/12/1687cuprizonedemyelinationmotor coordinationanxietysex differencesmultiple sclerosis
spellingShingle Kelly F. Paton
Sheein Hong
Andrew Biggerstaff
Bronwyn M. Kivell
Sex Differences in the Behavioural Aspects of the Cuprizone-Induced Demyelination Model in Mice
Brain Sciences
cuprizone
demyelination
motor coordination
anxiety
sex differences
multiple sclerosis
title Sex Differences in the Behavioural Aspects of the Cuprizone-Induced Demyelination Model in Mice
title_full Sex Differences in the Behavioural Aspects of the Cuprizone-Induced Demyelination Model in Mice
title_fullStr Sex Differences in the Behavioural Aspects of the Cuprizone-Induced Demyelination Model in Mice
title_full_unstemmed Sex Differences in the Behavioural Aspects of the Cuprizone-Induced Demyelination Model in Mice
title_short Sex Differences in the Behavioural Aspects of the Cuprizone-Induced Demyelination Model in Mice
title_sort sex differences in the behavioural aspects of the cuprizone induced demyelination model in mice
topic cuprizone
demyelination
motor coordination
anxiety
sex differences
multiple sclerosis
url https://www.mdpi.com/2076-3425/12/12/1687
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AT andrewbiggerstaff sexdifferencesinthebehaviouralaspectsofthecuprizoneinduceddemyelinationmodelinmice
AT bronwynmkivell sexdifferencesinthebehaviouralaspectsofthecuprizoneinduceddemyelinationmodelinmice