Maharjan Siddhartha, Kochman Eliyahu, Gervase Tatiana, Page Nina, Singh Mannut, Singh Rajveer, Chitnis Avani, Shah Ashka, Addepalli Sidharth, Paradkar Ria, Chavali Rishika, Mir Hana, Zheng Anna, Steenman Lydia, Shorrock Hannah, Berglund Andrew, Vedam-Mai Vinata, Shin Damian
Department of Neuroscience and Experimental Therapeutics, Albany medical College, 47 New Scotland Ave, Albany, NY, 12208, USA.
Department of Anatomical Sciences and Neurobiology, University of Louisville, 511 S. Floyd St. Room 111, Louisville, KY, 40202, USA.
Cerebellum. 2025 Sep 18;24(6):157. doi: 10.1007/s12311-025-01910-2.
Spinocerebellar ataxia 1 (SCA1) is a rare autosomal dominant neurodegenerative disease characterized by impaired gait, coordination, and balance. SCA1 results from an expanded CAG repeat in the Atxn1 gene, inducing protein aggregation and ultimately leading to the degeneration of cerebellar Purkinje cells. Clinical studies have shown that gait impairments, such as changes in stride length (SL), stride time, and stance phase, are seen in patients with cerebellar diseases. The SCA1 mouse model reflects the longitudinal progression of SCA1 in humans, displaying motor incoordination, muscle atrophy, and cerebellar Purkinje cell degradation. In this study, we aim to characterize the progression of gait impairments that arise in the SCA1 mouse model. The DigiGait™ system, which utilizes ventral plane imaging technology, was used to track gait parameters in SCA mice, beginning at 7 weeks of age until 42 weeks. Our data revealed that SCA males exhibited decreasing gait speeds beginning weeks 15-16 (p < 0.05), and SCA females showed gait speed declining as early as 9 weeks (p < 0.05). A decrease in SL was also found; these emerged at different time points in SCA1 mice, ranging from weeks 14 to 32. Our data also suggest that SCA1 mice have decreased loading speed in hindlimbs with lower MAX dA/dt values at weeks 30 and 40 in both males and females (p < 0.01). Our characterization of this model establishes a framework for sex- and age-related differences, as well as a timeline of various gait performance metrics, which provides a foundation to test the efficacy of novel therapeutics.
脊髓小脑共济失调1型（SCA1）是一种罕见的常染色体显性神经退行性疾病，其特征为步态、协调性和平衡受损。SCA1由Atxn1基因中的CAG重复序列扩增引起，导致蛋白质聚集，最终导致小脑浦肯野细胞变性。临床研究表明，小脑疾病患者会出现步态障碍，如步幅长度（SL）、步幅时间和站立期的变化。SCA1小鼠模型反映了SCA1在人类中的纵向进展，表现出运动不协调、肌肉萎缩和小脑浦肯野细胞退化。在本研究中，我们旨在描述SCA1小鼠模型中出现的步态障碍的进展情况。利用腹侧平面成像技术的DigiGait™系统用于跟踪SCA小鼠的步态参数，从7周龄开始直至42周。我们的数据显示，SCA雄性小鼠在第15 - 16周开始步态速度下降（p < 0.05），而SCA雌性小鼠早在9周时就显示步态速度下降（p < 0.05）。还发现步幅长度减小；这些在SCA1小鼠的不同时间点出现，范围从第14周到32周。我们的数据还表明，SCA1小鼠后肢的加载速度降低，在第30周和第40周时，雄性和雌性小鼠的最大dA/dt值均较低（p < 0.01）。我们对该模型的特征描述建立了一个与性别和年龄相关差异的框架，以及各种步态性能指标的时间线，这为测试新型疗法的疗效提供了基础。
