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

Author(s)

Serra-de-Oliveira, Nathalia ^{[1, 2]} ; Boilesen, Sabine Nunes ^[1] ; de Franca Carvalho, Carolina Prado ^[1] ; LeSueur-Maluf, Luciana ^[1] ; Zollner, Ricardo de Lima ^[3] ; Spadari, Regina Celia ^[1] ; Medalha, Carla Cristina ^[1] ; de Castro, Glaucia Monteiro ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, UNIFESP, Dept Biociencias, BR-11015020 Santos, SP - Brazil

^[2] Univ Fed Sao Paulo, UNIFESP, Programa Interdisciplinar Ciencias Saude, BR-11060001 Santos, SP - Brazil

^[3] Univ Estadual Campinas, UNICAMP, FCM, LIAE, BR-13083887 Campinas, SP - Brazil

• Document type: Journal article
• Source: Behavioural Brain Research; v. 287, p. 265-275, JUL 1 2015.
• Web of Science Citations: 14

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. (AU)

• FAPESP's process: 07/07828-3 - Characterization of the cuprizone-induced demyelization process in Lewis rat strain
• Grantee: Gláucia Monteiro de Castro
• Support Opportunities: Regular Research Grants