Early signs of neurolipidosis-related behavioural alterations in a murine model of metachromatic leukodystrophy

Arylsulfatase A (ASA)-deficient mice represent an animal model for the lysosomal storage disorder metachromatic leukodystrophy (MLD). Although the model has been applied in pathophysiological and therapeutic studies, the behavioural phenotype of ASA−/− mice is only partially characterized, and the m...

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Bibliographic Details
Published in:Behavioural brain research 2008-06, Vol.189 (2), p.306-316
Main Authors: Stroobants, Stijn, Leroy, Toon, Eckhardt, Matthias, Aerts, Jean-Marie, Berckmans, Daniel, D’Hooge, Rudi
Format: Article
Language:English
Subjects:
Age Factors
Animals
Avoidance Learning - physiology
Behavioral psychophysiology
Behavioural testing
Biological and medical sciences
Cerebellum - metabolism
Cerebellum - pathology
Cerebroside-Sulfatase - genetics
Cerebroside-Sulfatase - metabolism
Cerebrum - metabolism
Cerebrum - pathology
Conditioning, Operant - physiology
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Disease Models, Animal
Errors of metabolism
Exploratory Behavior - physiology
Female
Fundamental and applied biological sciences. Psychology
Gait - physiology
Gait analysis
Gait Ataxia - genetics
Gait Ataxia - pathology
Gait Ataxia - physiopathology
Inhibition (Psychology)
Leukodystrophy, Metachromatic - complications
Leukodystrophy, Metachromatic - genetics
Leukodystrophy, Metachromatic - physiopathology
Lipidoses - complications
Lipidoses - genetics
Lipidoses - physiopathology
Lipids (lysosomal enzyme disorders, storage diseases)
Lysosomal storage disorders
Male
Matched-Pair Analysis
Medical sciences
Metabolic diseases
Metachromatic leukodystrophy
Mice
Mice, Inbred C57BL
Mice, Knockout
Motor Activity - physiology
Mouse models
Neurology
Operant conditioning
Phenotype
Psychology. Psychoanalysis. Psychiatry
Psychology. Psychophysiology
Psychomotor Performance - physiology
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Summary:Arylsulfatase A (ASA)-deficient mice represent an animal model for the lysosomal storage disorder metachromatic leukodystrophy (MLD). Although the model has been applied in pathophysiological and therapeutic studies, the behavioural phenotype of ASA−/− mice is only partially characterized, and the most decisive outcome measures for therapy evaluation only emerge beyond 1 year of age. Presently, ASA−/− mice and ASA+/− control mice were studied at 6 and 12 months of age on an extensive battery including tests of neuromotor ability, exploratory behaviour, and learning and memory. Overt signs of ataxia were not observed in 6-month-old ASA−/− mice, but quantitative gait analysis during open-field exploration revealed that ASA−/− mice displayed increased hind base width and increased stride lengths for all paws. Their covert motor incoordination was evident in a correlation analysis which unveiled decreased harmonisation of concurrent gait parameters. For example, while ASA+/− controls demonstrated substantial convergence of front and hind base width (r=0.54), these variables actually diverged in ASA−/− mice (r=−0.37). Furthermore, various behavioural observations indicated emotional alterations in ASA−/− mice. Six-month-old ASA−/− mice also showed decreased response rates in scheduled operant responding. The present findings could provide relevant behavioural outcome measures for further use of this murine MLD model in preclinical studies.
ISSN:0166-4328
1872-7549
DOI:10.1016/j.bbr.2008.01.008