Evaluation of Potential Antioxidative Compounds and Natural Products Using SCA17 Transgenic Mice and Cerebellar Primary Culture

• Main Authors: Shiang-Wen Chen, 陳翔文
• Other Authors: Hsiu-Mei Hsieh
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/70852520173296245081

碩士 === 國立臺灣師範大學 === 生命科學研究所 === 102 === Spinocerebellar ataxia 17 (SCA17) is an autosomal dominant neurodegenerative disease caused by trinucleotide CAA/CAG repeat excessive expansion in TATA box Binding Protein (TBP) gene. Expanded CAA/CAG repeat encodes polyglutamine (polyQ) in TBP, which causes mutant polyQ proteins aggregate and the cerebellar Purkinje cell degeneration. Some effective treatments for neurodegenerative disease using Chinese herbs and anti-oxidants have been reported in cellular and animal studies. Our lab has generated SCA17 mouse model and used for potential therapeutic screening. We first used SCA17 transgenic mouse cerebellar primary to screen potential Chinese herbs and anti-oxidative compounds. Immunocytochemistry was conducted to stain Purkinje cell, and measured neurite outgrowth to evaluate the effect of treatment in cerebellar primary culture. The screening results showed two herbal extracts and three synthesized anti-oxidative compounds could increase neurite outgrowth on SCA17 cerebellar primary culture. In vivo treatment results showed that mouse body weight and spontaneous activity were unaffected under the treatment of anti-oxdative compounds. The motor coordination of mice on rotarod task was improved after treatment. We also found that heat shock proteins and superoxide dismutase were increased and Purkinje cell degeneration , mutant protein TBP aggregation and inflammation were attenuated after the treatment with these compounds. These anti-oxidative compounds have potential for SCA17 diseases treatment.