Treadmill training increases the motor activity and neuron survival of the cerebellum in a mouse model of spinocerebellar ataxia type 1

• Published in: The Kaohsiung journal of medical sciences Vol. 35; no. 11; pp. 679 - 685
• Main Authors: Chuang, Chieh‐Sen, Chang, Jui‐Chih, Soong, Bing‐Wen, Chuang, Sheng‐Fei, Lin, Ta‐Tsung, Cheng, Wen‐Ling, Orr, Harry T., Liu, Chin‐San
• Format: Journal Article
• Language: English
• Published: BP, Asia Wiley Publishing Asia Pty Ltd 01.11.2019; John Wiley & Sons, Inc; Wiley
• Subjects: Analysis; Animals; Autophagy; Basic Helix-Loop-Helix Transcription Factors - metabolism; Brain; Cell Count; Cell Survival; Cerebellum - pathology; Disease Models, Animal; Exercise; Genetic engineering; Mice, Inbred C57BL; Mice, Transgenic; Motor Activity; neuronal Per Arnt Sim domain protein 4; Neuronal Plasticity; Neurons; Neurons - metabolism; Neurons - pathology; Phosphorylation; Physical Conditioning, Animal; Purkinje Cells - pathology; Purkinje neurons; Pyrimidines; ribosomal protein S6; Ribosomal Protein S6 - metabolism; Signal Transduction; Spinocerebellar ataxia; Spinocerebellar ataxia type 1; Spinocerebellar Ataxias - pathology; Spinocerebellar Ataxias - physiopathology; TOR Serine-Threonine Kinases - metabolism; treadmill training; treadmill training; neuronal Per Arnt Sim domain protein 4; ribosomal protein S6; Spinocerebellar ataxia type 1; Purkinje neurons
• ISSN: 1607-551X; 2410-8650
• DOI: 10.1002/kjm2.12106

Spinocerebellar ataxia (SCA) type 1 (SCA1) is a rare autosomal dominant disorder that is characterized by worsening of disordered coordination, ataxia of the trunk, and other neurological symptoms. Physical activity improves both mobility and the daily living activities of patients with SCA. Intervention with daily regular treadmill exercise may slow the deterioration of cerebellar neurons in SCA1. Therefore, the signal changes and performance of cerebellar neurons after exercise in SCA1 was investigated in this study. We employed a transgenic mouse model of SCA1, generated by amplifying the cytosine‐adenine‐guanine trinucleotide repeat expansions, and the mice underwent 1 month of moderate daily treadmill exercise for 1 hour. The rotarod test revealed that the motor function of the SCA1 mice that underwent training was superior to that of the control SCA1 mice, which did not undergo training. Moreover, the cerebellar pathology revealed preserved Purkinje neurons stained by carbindin with an increase of the neuronal Per Arnt Sim domain protein 4, a key regulation in the structural and functional plasticity of neurons, in the excised SCA1 mice relative to the controls. The mechanism was related to an increase of phosphorylation of ribosomal protein S6, a downstream target of the mammalian target of rapamycin pathway, but not to autophagy activation. This study determined that regular treadmill exercise may play a crucial role in the viable support of cerebellar neurons in SCA1.