ECTRIMS eLearning

Expanding the behavioural characterization of the cuprizone mouse model: what changes will be most sensitive to early remyelination?
ECTRIMS Learn. Palavra F. 10/27/17; 200617; P962
Filipe Palavra
Filipe Palavra
Contributions
Abstract

Abstract: P962

Type: Poster

Abstract Category: Pathology and pathogenesis of MS - 13 Experimental models

Introduction: The administration of cuprizone (CPZ) to C57BL/6 mice during 5 weeks induces central nervous system demyelination, reproducing some biological aspects that are similar to human multiple sclerosis (MS). If the intoxication is stopped, there will be spontaneous remyelination, making this model useful for the study of this particular aspect in MS.
Objective: To deepen the behavioural characterization of this animal model, defining the changes that best characterize
1) the peak of the demyelination process and
2) the earlier phase of spontaneous remyelination, in order to identify the most relevant behavioural changes.
Material and methods: Two groups of male C57BL/6 mice (n=10 each) were fed an oral solution of CPZ (0.2%) for 5 weeks (W5); half of the animals were subsequently kept under treatment with the vehicle (water) for another 2 weeks (W7). A vehicle-treated group was used as a control. After 5 and 7 weeks, animals were subjected to a wide battery of tests comprising rotarod, open field, elevated-plus maze, Y-maze, novel object recognition and splash tests, evaluating animals' locomotor ability, coordination, anxiety levels, explorative behaviour, spatial and long-term memory and mood state. Differences were considered for a 95% confidence interval (p< 0.05).
Results: No phenotypical differences were observed between CPZ-exposed and control animals at W5 (peak of demyelination), regarding motor skills, short- and long-term memory dysfunction and anxiety. However, trends for a difference were observed, considering explorative behaviour and anhedonia (using the open field and the splash tests) that were reversed at W7 (earliest phase of remyelination).
Conclusion: Explorative behaviour and animals' mood seem to be the first domains to be affected by CPZ intoxication and recovered during the remyelination process. Despite needing further confirmation in a larger set of animals, these are relevant data for the definition of the most sensitive behavioural changes to future pharmacological intervention.
Disclosure: Portuguese Foundation for Science and Technology (Strategic Projects Pest-C/SAU/UI3282/2013 and UID/NEU/04539/2013), COMPETE (POCI-01-0145-FEDER-007440) and Biogen.

Abstract: P962

Type: Poster

Abstract Category: Pathology and pathogenesis of MS - 13 Experimental models

Introduction: The administration of cuprizone (CPZ) to C57BL/6 mice during 5 weeks induces central nervous system demyelination, reproducing some biological aspects that are similar to human multiple sclerosis (MS). If the intoxication is stopped, there will be spontaneous remyelination, making this model useful for the study of this particular aspect in MS.
Objective: To deepen the behavioural characterization of this animal model, defining the changes that best characterize
1) the peak of the demyelination process and
2) the earlier phase of spontaneous remyelination, in order to identify the most relevant behavioural changes.
Material and methods: Two groups of male C57BL/6 mice (n=10 each) were fed an oral solution of CPZ (0.2%) for 5 weeks (W5); half of the animals were subsequently kept under treatment with the vehicle (water) for another 2 weeks (W7). A vehicle-treated group was used as a control. After 5 and 7 weeks, animals were subjected to a wide battery of tests comprising rotarod, open field, elevated-plus maze, Y-maze, novel object recognition and splash tests, evaluating animals' locomotor ability, coordination, anxiety levels, explorative behaviour, spatial and long-term memory and mood state. Differences were considered for a 95% confidence interval (p< 0.05).
Results: No phenotypical differences were observed between CPZ-exposed and control animals at W5 (peak of demyelination), regarding motor skills, short- and long-term memory dysfunction and anxiety. However, trends for a difference were observed, considering explorative behaviour and anhedonia (using the open field and the splash tests) that were reversed at W7 (earliest phase of remyelination).
Conclusion: Explorative behaviour and animals' mood seem to be the first domains to be affected by CPZ intoxication and recovered during the remyelination process. Despite needing further confirmation in a larger set of animals, these are relevant data for the definition of the most sensitive behavioural changes to future pharmacological intervention.
Disclosure: Portuguese Foundation for Science and Technology (Strategic Projects Pest-C/SAU/UI3282/2013 and UID/NEU/04539/2013), COMPETE (POCI-01-0145-FEDER-007440) and Biogen.

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