Edaravone is a mitochondrially targeted drug with a suggested capability to modify the course of diverse neurological diseases. Nevertheless, edaravone has not been tested yet in the context of spinocerebellar ataxia 1 (SCA1), an incurable neurodegenerative disease characterized mainly by cerebellar disorder, with a strong contribution of inflammation and mitochondrial dysfunction. This study aimed to address this gap, exploring the potential of edaravone to slow down SCA1 progression in a mouse knock-in SCA1 model. SCA1154Q/2Q and healthy SCA12Q/2Q mice were administered either edaravone or saline daily for more than 13 weeks. The functional impairments were assessed via a wide spectrum of behavioral assays reflecting motor and cognitive deficits and behavioral abnormalities. Moreover, we used high-resolution respirometry to explore mitochondrial function, and immunohistochemical and biochemical tools to assess the magnitude of neurodegeneration, inflammation, and neuroplasticity. Data were analyzed using (hierarchical) Bayesian regression models, combined with the methods of multivariate statistics. Our analysis pointed out various previously documented neurological and behavioral deficits of SCA1 mice. However, we did not detect any plausible therapeutic effect of edaravone on either behavioral dysfunctions or other disease hallmarks in SCA1 mice. Thus, our results did not provide support for the therapeutic potential of edaravone in SCA1.

Department of Pathological Physiology Faculty of Medicine in Pilsen Charles University alej Svobody 76 323 00 Pilsen Czech Republic

Department of Physiology Faculty of Medicine in Pilsen Charles University alej Svobody 76 323 00 Pilsen Czech Republic

Laboratory of Experimental Neurophysiology Biomedical Center Faculty of Medicine in Pilsen Charles University alej Svobody 76 323 00 Pilsen Czech Republic

Laboratory of Neurodegenerative Disorders Biomedical Center Faculty of Medicine in Pilsen Charles University alej Svobody 76 323 00 Pilsen Czech Republic

Mitochondrial Laboratory Biomedical Center Faculty of Medicine in Pilsen Charles University alej Svobody 76 323 00 Pilsen Czech Republic

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Lurcher Mouse as a Model of Cerebellar Syndromes