Nest-building Behavior Test in Mouse Models of Stroke

At a glance

    Introduction of Nest-building Behavior Test in Mouse Models of Stroke

    Ischemic stroke is a leading cause of death and disability, but translating experimental stroke research into effective clinical therapies has been challenging. A major reason for this may be the significant differences in functional tests and outcomes between animal stroke studies and clinical trials.

    Many functional or behavioral tests in animal studies are not designed to assess the natural behavior of animals but rather force the animal to perform tasks designed by researchers. Sensorimotor dysfunction is the most prominent clinical stroke deficit but mice can adapt to and therefore rapidly recover from sensorimotor deficits after stroke. Thus, some sensorimotor tests may be less sensitive in rodent stroke models, especially at late time points. Therefore, there is an urgent need to develop validated methods of assessing natural function for use in animal studies that reflect short- and long-term deficits in human stroke patients.

    Nest building activity can be a sensitive measure of long-term sensorimotor function, cognitive function, and overall health after stroke in mice. This method is expected to enhance the assessment of stroke deficits and recovery, providing a more natural and reliable assessment of functional outcomes in animal studies.

    Fig. 1. Illustrates the assessment of nest-building behavior as an indicator of stroke-related deficits in the mouse model of middle cerebral artery occlusion (MCAO).Fig.1. Evaluation of nest-building activity for indexing stroke deficits in the mouse MCAO model. (Yuan, et al., 2018)

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    What is the Nest Building Test

    Nest building is a natural behavior in the animal kingdom. For small mice, nests are important not only for warmth but also for reproduction and shelter. In order to construct suitable nests, mice must be able to perform a complex set of behaviors that depend on the functional integrity of their sensory and motor systems.

    The nest building test is a simple, inexpensive, and quantitative test that can be used to assess long-term sensory-motor function, cognitive function, and health after stroke in mice.

    Advantages of Nest Building Test

    • Nest building is performed in a cage and do not require the presence of an experimenter
    • Nest building in rodents is a spontaneous behavior that does not require artificial coercion
    • Bedding material that is not used can be weighted to obtain an objective measure
    • Simple to perform, but gives reliable readings

    Factors Affecting Nest Building in Mice

    Nest building in mice is influenced by environmental factors, particularly the choice of nest materials and bedding. Mice will build better nests dependent on the potential of the material, including structural integrity and amount and the potential for better insulation.

    For example, mice create more complex nests using shredded paper compared to compressed cotton nestlets. While nestlets have been shown to produce consistently good nests, the type of bedding is crucial. Mice build effective nests when using sawdust as bedding, as they incorporate it into their nests. In contrast, they struggle to create adequate nests with corn cob bedding. This emphasizes the importance of selecting appropriate nest materials and bedding for optimal nest-building outcomes in experimental settings.

    Nest Building Behavior Test in Mouse Models of Stroke

    Normal and middle cerebral artery occlusion (MCAO) mice are individually housed in cages containing wood chip bedding and one square of pressed cotton. No other nesting material is provided. The next morning, the mice and the nests in the cages are photographed and the manipulation of the nestle and the quality of the built nest are assessed manually according to a five-point scale.

    Fig. 2. Scoring criteria of nest building behavior test.Fig. 2. Scoring criteria. (Kraeuter, et al., 2019)

    References
    1. Yuan, D., et al. (2018). Nest‐building activity as a reproducible and long‐term stroke deficit test in a mouse model of stroke. Brain and behavior8(6), e00993.
    2. Kraeuter, A. K., et al. (2019). The nest building test in mice for assessment of general well-being. Pre-Clinical Models: Techniques and Protocols, 87-91.
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