Impaired muscle uptake of creatine in spinal and bulbar muscular atrophy
Hijikata Y, Katsuno M, Suzuki K, Hashizume A, Araki A, Yamada S, Inagaki T, Iida M, Noda S, Nakanishi H, Banno H, Mano T, Hirakawa A, Adachi H, Watanabe H, Yamamoto M, Sobue G
Annals of clinical and translational neurology · 34 citations
How it was studied
- Design
- Cross-sectional study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- Japan Agency for Medical Research and Development
- Government
- Ministry of Education, Culture, Sports, Science and Technology
- Nonprofit
- Foundation of Synapse and Neurocircuit Pathology
- Nonprofit
- Kanae Foundation for the Promotion of Medical Science
- Government
- Japan Society for the Promotion of Science
- Government
- Japan Science and Technology Agency
- Unclassified
- Core Research for Evolutional Science and Technology
- Government
- Ministry of Education, Culture, Sports, Science, and Technology
- Grants
- Japan Agency for Medical Research and Development (15ek0109165); Japan Science and Technology Agency (CREST); Japan Agency for Medical Research and Development (CREST); Ministry of Education, Culture, Sports, Science and Technology (26670439); Japan Society for the Promotion of Science (26670440); Japan Society for the Promotion of Science (26670439); Ministry of Education, Culture, Sports, Science and Technology (15K15337); Ministry of Education, Culture, Sports, Science and Technology (26670440); Ministry of Education, Culture, Sports, Science and Technology (26293206); Ministry of Education, Culture, Sports, Science and Technology (22110005); Japan Society for the Promotion of Science (15K15337); Japan Society for the Promotion of Science (26293206); Japan Society for the Promotion of Science (CREST); Japan Society for the Promotion of Science (26117002); Japan Society for the Promotion of Science (26117001)
Based on 8 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2016-06-23 · Ann Clin Transl Neurol · vol. 3 · issue 7 · pp. 537–546
- Publisher
- Wiley
- Cited
- 47 citations · more than 93% of similar papers · 3.6× the field average
- Impact
- Top 10% most cited in its field
- References
- 44 works
- Access
- Open access (journal) · CC-BY-NC-ND
- Research areas
- Genetic Neurodegenerative Diseases · Muscle metabolism and nutrition · Amyotrophic Lateral Sclerosis Research
- Keywords
- Medicine, Spinal muscular atrophy, Creatine, Muscle contracture, Atrophy, Progressive muscular atrophy, Physical medicine and rehabilitation, Spinal and bulbar muscular atrophy, Muscle atrophy, Physical therapy, Pathology, Anatomy, Internal medicine, Amyotrophic lateral sclerosis, Disease
17 authors
From JP
- Yasuhiro HijikataNagoya University
- Masahisa Katsuno · correspondingNagoya University
- Keisuke SuzukiNational Center for Geriatrics and Gerontology; Nagoya University
- Atsushi HashizumeNagoya University
- Amane ArakiNagoya University
- Shinichiro YamadaNagoya University
Abstract
Objective
The aim of this study was to explore the pathomechanism underlying the reduction of serum creatinine (Cr) concentrations in spinal and bulbar muscular atrophy (SBMA).
Methods
We evaluated blood chemistries, motor function, and muscle mass measured by dual-energy X-ray absorptiometry in male subjects with SBMA (n = 65), amyotrophic lateral sclerosis (ALS; n = 27), and healthy controls (n = 25). We also examined the intramuscular concentrations of creatine, a precursor of Cr, as well as the protein and mRNA expression levels of the creatine transporter (SLC6A8) in autopsy specimens derived from subjects who had SBMA and ALS and disease controls. Furthermore, we measured the mRNA expression levels of SLC6A8 in cultured muscle cells (C2C12) transfected with the polyglutamine-expanded androgen receptor (AR-97Q).
Results
Serum Cr concentrations were significantly lower in subjects with SBMA than in those with ALS (P < 0.001), despite similar muscle mass values. Intramuscular creatine concentrations were also lower in with the autopsied specimen of SBMA subjects than in those with ALS subjects (P = 0.018). Moreover, the protein and mRNA expression levels of muscle SLC6A8 were suppressed in subjects with SBMA. The mRNA levels of SLC6A8 were also suppressed in C2C12 cells bearing AR-97Q.
Interpretation
These results suggest that low serum Cr concentration in subjects with SBMA is caused by impaired muscle uptake of creatine in addition to being caused by neurogenic atrophy. Given that creatine serves as an energy source in skeletal muscle, increasing muscle creatine uptake is a possible therapeutic approach for treating SBMA.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC-ND).
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