Department of Pathological Physiology, 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.
Int J Mol Sci. 2023 Jun 26;24(13):10689. doi: 10.3390/ijms241310689.
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. SCA1 and healthy SCA1 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.
依达拉奉是一种靶向线粒体的药物，据称具有改变多种神经疾病进程的能力。然而，依达拉奉尚未在脊髓小脑共济失调 1 型（SCA1）中进行测试，SCA1 是一种不可治愈的神经退行性疾病，主要表现为小脑障碍，炎症和线粒体功能障碍的强烈贡献。本研究旨在解决这一空白，探讨依达拉奉在 SCA1 小鼠基因敲入模型中减缓 SCA1 进展的潜力。SCA1 和健康 SCA1 小鼠每天接受依达拉奉或生理盐水治疗超过 13 周。通过广泛的行为评估来评估功能障碍，这些评估反映了运动和认知缺陷以及行为异常。此外，我们使用高分辨率呼吸测定法来探索线粒体功能，以及免疫组织化学和生化工具来评估神经退行性变，炎症和神经可塑性的程度。使用（分层）贝叶斯回归模型分析数据，并结合多变量统计方法。我们的分析指出了 SCA1 小鼠以前记录的各种神经和行为缺陷。然而，我们没有发现依达拉奉对 SCA1 小鼠的行为功能障碍或其他疾病特征有任何合理的治疗作用。因此，我们的结果并未为依达拉奉在 SCA1 中的治疗潜力提供支持。
