Trehalose Attenuates the Gait Ataxia and Gliosis of Spinocerebellar Ataxia Type 17 Mice

Zhi Zhong Chen, Chien Ming Wang, Guan Chiun Lee, Ho Chiang Hsu, Tzu Ling Wu, Chia Wei Lin, Chih Kang Ma, Guey Jen Lee-Chen, Hei Jen Huang, Hsiu Mei Hsieh-Li

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Spinocerebellar ataxia type 17 (SCA17) is caused by CAG/CAA repeat expansion on the gene encoding a general transcription factor, TATA-box-binding protein (TBP). The CAG repeat expansion leads to the reduced solubility of polyglutamine TBP and induces aggregate formation. The TBP aggregation, mostly present in the cell nuclei, is distinct from that in most other neurodegenerative diseases, in which the aggregation is formed in cytosol or extracellular compartments. Trehalose is a disaccharide issued by the Food and Drug Administration with a Generally Recognized As Safe status. Lines of evidence suggest trehalose could prevent protein aggregate formation in several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. In this study, we evaluated the therapeutic potential of trehalose on SCA17 using cerebellar primary and organotypic culture systems and a mouse model. Our results showed that TBP nuclear aggregation was significantly decreased in both the primary and slice cultures. Trehalose (4 %) was further supplied in the drinking water of SCA17 transgenic mice. We found both the gait behavior in the footprint analysis and motor coordination in the rotarod task were significantly improved in the trehalose-treated SCA17 mice. The cerebellar weight was increased and the astrocyte gliosis was reduced in SCA17 mice after trehalose treatment. These data suggest that trehalose could be a potential nontoxic treatment for SCA17.

Original languageEnglish
Pages (from-to)800-810
Number of pages11
JournalNeurochemical Research
Volume40
Issue number4
DOIs
Publication statusPublished - 2015 Jan 1

Keywords

  • Intranuclear aggregation
  • Spinocerebellar ataxia
  • TBP
  • Trehalose

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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