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

Chieh Sen Chuang, Jui Chih Chang, Bing Wen Soong, Sheng Fei Chuang, Ta Tsung Lin, Wen Ling Cheng, Harry T. Orr, Chin San Liu

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10 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)679-685
Number of pages7
JournalKaohsiung Journal of Medical Sciences
Issue number11
StatePublished - Nov 1 2019

Bibliographical note

Funding Information:
We are thankful to Prof. Harry T. Orr in the Department of Laboratory Medicine and Pathology and Director of the Institute for Translational Neuroscience at the University of Minnesota, USA for providing animal sources and Mr. Casey, an intern of Vascular and Genomic Center, for the assistance in animal training.

Publisher Copyright:
© 2019 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.


  • Purkinje neurons
  • Spinocerebellar ataxia type 1
  • neuronal Per Arnt Sim domain protein 4
  • ribosomal protein S6
  • treadmill training


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