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

• Published in: Behavioural brain research 2015-07, Vol.287, p.265-275
• Main Authors: Serra-de-Oliveira, Nathalia, Boilesen, Sabine Nunes, Prado de França Carvalho, Carolina, LeSueur-Maluf, Luciana, Zollner, Ricardo de Lima, Spadari, Regina Célia, Medalha, Carla Cristina, Monteiro de Castro, Gláucia
• Format: Article
• Language: English
• Subjects: Animals; Anxiety - chemically induced; Anxiety - physiopathology; Behavior, Animal - drug effects; Behaviour; Cognition; Corpus Callosum - pathology; Cuprizone; Cuprizone - toxicity; Disease Models, Animal; Encephalitis - metabolism; Humans; Male; Microglia - cytology; Microglia - drug effects; Motor Activity - drug effects; Multiple Sclerosis - chemically induced; Multiple Sclerosis - pathology; Multiple Sclerosis - psychology; Myelin Sheath - pathology; Neuroinflammation; Oligodendroglia - drug effects; Oligodendroglia - metabolism; Rats; Rats, Inbred Lew; White matter; White Matter - pathology
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2015.03.038

•The demyelination induced by cuprizone in Lewis rats induces anxiety-like behaviour.•The demyelination leads to cognitive impairment.•Behavioural changes and neuroinflammation in Lewis rats share some similarities to those seen in human patients with white matter damage. 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.