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KMID : 0613820220320080611
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Journal of Life Science
2022 Volume.32 No. 8 p.611 ~ p.621
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DMSO Improves Motor Function and Survival in the Transgenic SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis
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Park Kyung-Ho
Kim Yeon-Gyeong
Park Hyun-Woo
Lee Hee-Young
Lee Jeong-Hoon
Sweeney Patrick
Park Larry Chong
Park Jin-Kyu
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Abstract
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Dimethyl sulfoxide (DMSO) is commonly used as control or vehicle solvent in preclinical research of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) due to its ability to dissolve lipophilic compounds and cross the blood brain barrier. However, the biochemical effects of DMSO on the outcomes of preclinical research are often overlooked. In the present study, we investigated whether the long-term oral administration of 5% DMSO affects the neurological, functional, and histological disease phenotype of the copper/zinc superoxide dismutase glycine 93 to alanine mutation (SOD1-G93A) mouse model of amyotrophic lateral sclerosis. SOD1-G93A transgenic mice showed shortened survival time and reduced motor function. We found that administration with DMSO led to increased mean survival time, reduced neurological scores, and improved motor performance tested using the rotarod and grip strength tests. On the other hand, DMSO treatment did not attenuate motor neuron loss in the spinal cord and denervation of neuromuscular junctions in the skeletal muscle. These results suggest that DMSO administration could improve the quality of life of the SOD1-G93A mouse model of ALS without affecting motor neuron denervation. In conclusion, the use of DMSO as control or vehicle solvent in preclinical research may affect the behavioral outcomes in the SOD1-G93A mouse model. The effect of the vehicle should be thoroughly considered when interpreting therapeutic efficacy of candidate drugs in preclinical research.
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KEYWORD
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ALS, antioxidant, DMSO, neuroprotection, SOD1-G93A, vehicle
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