Behavioural changes observed in demyelination model shares similarities with white matter abnormalities in humans

Behavioural changes observed in demyelination model shares similarities with white matter abnormalities in humans

Author Serra-de-Oliveira, Nathalia Autor UNIFESP Google Scholar
Boilesen, Sabine Nunes Autor UNIFESP Google Scholar
Franca Carvalho, Carolina Prado de Autor UNIFESP Google Scholar
LeSueur-Maluf, Luciana Autor UNIFESP Google Scholar
Zollner, Ricardo de Lima Google Scholar
Spadari, Regina Celia Autor UNIFESP Google Scholar
Medalha, Carla Cristina Autor UNIFESP Google Scholar
Castro, Glaucia Monteiro de Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade Estadual de Campinas (UNICAMP)
Abstract Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS). Further to the symptoms resulting from demyelination, new studies point to the involvement of neuroinflammation and white matter abnormalities in psychiatric disorders and neurodegenerative diseases. Cuprizone, a model of MS, produces consistent demyelination and elicits behavioural, morphological and inflammatory changes in animals that share some similarities with those observed in humans. in this study, we used the cuprizone model in Lewis rats to evaluate clinical signs triggered by the demyelination process which could be comparable with the symptoms seen in white matter abnormalities in human beings. To induce the demyelination process, 0.6% cuprizone was added to the Lewis rats' diet for 4 weeks. We proceeded with behavioural, morphological and immunological analyses. Animals fed with cuprizone exhibited behavioural changes: higher scores in the neurotoxicity test, reduced exploratory and locomotion behaviour, and also an increase of permanency in the closed arm of the elevated plus maze test, were observed. in these analyses, the animals showed motor coordination impairment and anxiety-like behaviour. Demyelination also triggered changes in discrimination of objects identified by an increase in the time spent close to a familiar object. These behavioural alterations were associated with a significant increase in the levels of TNF-alpha and corticosterone, consistent with the activation of microglia and astrocytes. Taken together, the results of this work show the cuprizone/Lewis rat model demyelination as an attractive paradigm for studying the correlation between white matter abnormalities and behaviour. (C) 2015 Elsevier B.V. All rights reserved.
Keywords Behaviour
Cognition
Cuprizone
Neuroinflammation
White matter
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Grant number FAPESP: 07/07828-3
Date 2015-07-01
Published in Behavioural Brain Research. Amsterdam: Elsevier B.V., v. 287, p. 265-275, 2015.
ISSN 0166-4328 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 265-275
Origin http://dx.doi.org/10.1016/j.bbr.2015.03.038
Access rights Closed access
Type Article
Web of Science ID WOS:000355037700034
URI http://repositorio.unifesp.br/handle/11600/39148

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