LA - ICVS/3B's - Associate Laboratory

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Digital Ventilated Cages (DVC®) as a tool for the study of Machado-Joseph Disease

Publication . Santos, Alexandre José Pinto; Carlos, Magda João Castelhano; Silva, Sara Carina Duarte; Cristóvão, Ana Clara

DVC® (Digital Ventilated Cage), a home-cage rack monitoring system is capable of continuously detecting spontaneous animal activity occurring in their home cage 24/7. This monitoring allows a non-intrusive study, providing a better welfare and a potential improvement in experimental reproducibility. In this study, we evaluated the influence of physical exercise as a therapeutic strategy to improve motor dysfunction in a mouse model of Machado–Joseph Disease (MJD), the CMVMJD135. MJD is the most common autosomal dominant ataxia worldwide, a neurodegenerative disorder caused by a CAG repeat expansion within the Ataxin-3 gene, causing mostly motor symptoms. The clinical variability of the disease phenotype as well as the age of onset depend on the length of the expanded repeat. The CMVMJD135 resembles the human disorder both at the behavioral and pathological levels. In this study, the mice were divided into 4 groups (Wild-Type (WT); Transgenic (TG); Wild-Type with Running Wheel (WTRW); Transgenic with Running Wheel (TGRW)), with a distribution of 2 animals per cage. The DVC® automatically collected data on spontaneous activity in the cage and voluntary physical exercise on the Running wheel (RW). Additionally, other motorrelated tests were performed, which are usually the standard for characterizing the disease establishment and progression in MJD mouse models, to understand the influence of spontaneous activity within the cage and the performance in the RW by each group. The analysis of the overall animals’ activity during the night period showed that TG mice had significant less activity when compared to their WT-littermates. Additionally, TG mice with access to RW where more active than TG mice without RW. As for the exercise practiced on the RW, the WT group showed much higher values compared to TG. Regarding the additional behavior tests, the overall results showed a tendency for the TG mice with access to the Running Wheel to present a better performance when compared to TG without RW. Overall, these results suggest that the DVC® system is able to detect the phenotype of the MJD mice without the experimenter interference and the presence of running wheels in the cages seem to improve their motor phenotype. These promising results point to further and more extensive characterization of physical exercise in this mouse model. Furthermore, this automated system may be of great importance to other models of disease, being a complementary tool to animal behavior testing.

2021-03-29Master thesis

Open access