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Motor Behavioral Deficits in the Cuprizone Model: Validity of the Rotarod Test Paradigm
Concordia Lubrich1, Paula Giesler1, Markus Kipp1
1Institute of Anatomy, Rostock University Medical Center, 18057 Rostock, Germany.
Abstract:
Multiple Sclerosis (MS) is a neuroinflammatory disorder, which is histopathologically characterized by multifocal inflammatory demyelinating lesions affecting both the central nervous system's white and grey matter. Especially during the progressive phases of the disease, immunomodulatory treatment strategies lose their effectiveness. To develop novel progressive MS treatment options, pre-clinical animal models are indispensable. Among the various different models, the cuprizone de- and remyelination model is frequently used. While most studies determine tissue damage and repair at the histological and ultrastructural level, functional readouts are less commonly applied. Among the various overt functional deficits, gait and coordination abnormalities are commonly observed in MS patients. Motor behavior is mediated by a complex neural network that originates in the cortex and terminates in the skeletal muscles. Several methods exist to determine gait abnormalities in small rodents, including the rotarod testing paradigm. In this review article, we provide an overview of the validity and characteristics of the rotarod test in cuprizone-intoxicated mice.
Insights
The rotarod test effectively assesses gait abnormalities in mice with Multiple Sclerosis (MS) during demyelination and remyelination phases. This functional readout is crucial for developing new progressive MS treatments.
Area of Science:
- Neuroscience
- Immunology
- Animal Models
Background:
- Multiple Sclerosis (MS) is a neuroinflammatory disease impacting central nervous system white and grey matter.
- Current immunomodulatory treatments are less effective in progressive MS phases.
- Pre-clinical models are vital for developing novel progressive MS therapies.
Purpose of the Study:
- To review the validity and characteristics of the rotarod test.
- To evaluate the rotarod test as a functional readout in cuprizone-induced demyelination/remyelination models.
Main Methods:
- Cuprizone intoxication model in mice.
- Assessment of gait and coordination abnormalities using the rotarod test.
- Review of existing literature on rotarod testing in MS models.
Main Results:
- Gait and coordination deficits are common functional deficits in MS patients.
- The rotarod test is a valuable method for detecting motor behavior abnormalities in rodents.
- The rotarod test demonstrates validity in cuprizone-intoxicated mice.
Conclusions:
- The rotarod test is a relevant functional readout for studying MS.
- This method aids in evaluating therapeutic strategies in pre-clinical MS models.
- Further application of functional readouts like the rotarod test is recommended for progressive MS research.
