title: Impaired muscle uptake of creatine in spinal and bulbar muscular atrophy.
abstract: 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).
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Neurology Nagoya University Graduate School of Medicine Nagoya Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hijikata
authors.affiliation: Department of Neurology Nagoya University Graduate School of Medicine Nagoya Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Katsuno
authors.affiliation: Department of Neurology Nagoya University Graduate School of Medicine Nagoya Japan; Innovation Center for Clinical Research National Center for Geriatrics and Gerontology Obu Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Neurology Nagoya University Graduate School of Medicine Nagoya Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hashizume
authors.affiliation: Department of Neurology Nagoya University Graduate School of Medicine Nagoya Japan.
authors.forename: Amane
authors.initials: A
authors.lastname: Araki
authors.affiliation: Department of Neurology Nagoya University Graduate School of Medicine Nagoya Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Neurology Nagoya University Graduate School of Medicine Nagoya Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Inagaki
authors.affiliation: Department of Neurology Nagoya University Graduate School of Medicine Nagoya Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Iida
authors.affiliation: Department of Neurology Nagoya University Graduate School of Medicine Nagoya Japan.
authors.forename: Seiya
authors.initials: S
authors.lastname: Noda
authors.affiliation: Department of Neurology Nagoya University Graduate School of Medicine Nagoya Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Nakanishi
authors.affiliation: Department of Neurology Nagoya University Graduate School of Medicine Nagoya Japan; Institute for Advanced Research Nagoya University Nagoya Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Banno
authors.affiliation: Department of Neurology Nagoya University Graduate School of Medicine Nagoya Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Mano
authors.affiliation: Biostatistics Section, Center for Advanced Medicine and Clinical Research Nagoya University Graduate School of Medicine Nagoya Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hirakawa
authors.affiliation: Department of Neurology Nagoya University Graduate School of Medicine Nagoya Japan; Department of Neurology University of Occupational and Environmental Health School of Medicine Kitakyushu Japan.
authors.forename: Hiroaki
authors.identifier: 0000-0002-9302-4663
authors.initials: H
authors.lastname: Adachi
authors.affiliation: Department of Neurology Nagoya University Graduate School of Medicine Nagoya Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Speech Pathology and Audiology Aichi-Gakuin University School of Health Science Nisshin Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Neurology Nagoya University Graduate School of Medicine Nagoya Japan; Research Division of Dementia and Neurodegenerative Disease Nagoya University Graduate School of Medicine Nagoya Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue