Sucha 2023 Int J Mol Sci
| Sucha M, Benediktova S, Tichanek F, Jedlicka J, Kapl S, Jelinkova D, Purkartova Z, Tuma J, Kuncova J, Cendelin J (2023) Experimental treatment with edaravone in a mouse model of spinocerebellar ataxia 1. https://doi.org/10.3390/ijms241310689 |
» Int J Mol Sci 24(13):10689. PMID: 37445867 Open Access
Sucha Martina, Benediktova Simona, Tichanek Filip, Jedlicka Jan, Kapl Stepan, Jelinkova Dana, Purkartova Zdenka, Tuma Jan, Kuncova Jitka, Cendelin Jan (2023) Int J Mol Sci
Abstract: 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. • Keywords: cerebellum, edaravone, mitochondria, neurodegeneration, spinocerebellar ataxia type 1
• O2k-Network Lab: CZ Pilsen Kuncova J
Labels: MiParea: Respiration, Pharmacology;toxicology
Pathology: Neurodegenerative
Organism: Mouse Tissue;cell: Nervous system Preparation: Homogenate
Pathway: N, S, CIV, NS, ROX HRR: Oxygraph-2k
