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Behav Brain Res. 2019 May 2;363:38-44. doi: 10.1016/j.bbr.2019.01.036. Epub 2019 Jan 28.

Long lasting behavioural effects on cuprizone fed mice after neurotoxicant withdrawal.

Author information

1
Girona Neuroimmunology and Multiple Sclerosis Unit (UNIEMTG), Dr. Josep Trueta University Hospital and Neurodegeneration and Neuroinflammation Research Group, Girona Biomedical Research Institute (IDIBGI), Spain. Electronic address: jtomas@idibgi.org.
2
Dept. of Psychology, Universitat Rovira i Virgili, Tarragona, Spain; Research Center for Behavior Assessment (CRAMC), Universitat Rovira i Virgili, Tarragona, Spain; Laboratory of Toxicology and Environmental Health, School of Medicine, Reus, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain.
3
Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain; Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain; Dept. of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
4
Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain; Hospital Universitari Institut Pere Mata, IISPV. Universitat Rovira i Virgili, Reus, Spain; Centro de Investigación Biomédica en Red (CIBER) en Salud Mental, Reus, Spain.
5
Dept. of Psychology, Universitat Rovira i Virgili, Tarragona, Spain; Research Center for Behavior Assessment (CRAMC), Universitat Rovira i Virgili, Tarragona, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain; Research in Neurobehavior and Health (NEUROLAB), Universitat Rovira i Virgili, Tarragona, Spain.

Abstract

Destruction of the myelin sheath in the central nervous system (CNS) is prominent in many clinico-pathologic conditions. Among animal models that reproduce the pathological features of de- and remyelination processes, the mouse model of cuprizone administration is widely used. Both hyperactivity and motor impairment have been reported upon cuprizone exposure. The aim of the present study was to assess behaviour in mice after CPZ withdrawal.To summarize, animals showed hypo-activity and deficits in motor coordination when they were subjected to acute demyelinating insult while minor exploratory activity, impairment in motor coordination and lower anxiety levels emerged when remyelination was reached following cuprizone withdrawal. A recovery period of 6 weeks after removal of CPZ was not accompanied by a similar return of normal activity indicating long lasting behavioural effects caused by this neurotoxicant. Specifically, the recovery group showed impairments in neurological functions involved in sensorimotor, neuromuscular, motor coordination and the capacity to cope with a stress-inducing event.

KEYWORDS:

Cuprizone; Demyelination; Motor coordination and anxiety; Neurobehavioral screening; Remyelination

PMID:
30703396
DOI:
10.1016/j.bbr.2019.01.036

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