Decreased Peak Expiratory Flow Associated with Muscle Fiber-Type Switching in Spinal and Bulbar Muscular Atrophy

• Published in: PloS one Vol. 11; no. 12; p. e0168846
• Main Authors: Yamada, Shinichiro, Hashizume, Atsushi, Hijikata, Yasuhiro, Inagaki, Tomonori, Suzuki, Keisuke, Kondo, Naohide, Kawai, Kaori, Noda, Seiya, Nakanishi, Hirotaka, Banno, Haruhiko, Hirakawa, Akihiro, Koike, Haruki, Halievski, Katherine, Jordan, Cynthia L., Katsuno, Masahisa, Sobue, Gen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.12.2016; Public Library of Science (PLoS)
• Subjects: Activities of daily living; Adult; Aged; Aged, 80 and over; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - metabolism; Amyotrophic Lateral Sclerosis - physiopathology; Androgens; Atrophy; Biology and Life Sciences; Care and treatment; Comparative analysis; Complications and side effects; Diagnosis; Disease control; Disease Progression; Dyspnea; Fibers; Gene expression; Humans; Immunofluorescence; Kinases; Male; Medicine; Medicine and Health Sciences; Middle Aged; Mitochondria; mRNA; Muscle Fibers, Skeletal - metabolism; Muscle Fibers, Skeletal - physiology; Muscle proteins; Muscle Strength; Muscles; Muscular atrophy; Muscular Atrophy, Spinal - metabolism; Muscular Atrophy, Spinal - physiopathology; Muscular Disorders, Atrophic - metabolism; Muscular Disorders, Atrophic - physiopathology; Musculoskeletal system; Myosin; Neurology; Neurosciences; Peak Expiratory Flow Rate; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism; Physiological aspects; Polymerase chain reaction; PPAR delta - metabolism; Proteins; Respiratory function; Respiratory Function Tests; RNA, Messenger - metabolism; Rodents; Skeletal muscle; Spinal and bulbar muscular atrophy; Spinal cord; Tongue; University graduates; United States; East Lansing Michigan; United States > US; Japan; Michigan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0168846

The aim of this study was to characterize the respiratory function profile of subjects with spinal and bulbar muscular atrophy (SBMA), and to explore the underlying pathological mechanism by comparing the clinical and biochemical indices of this disease with those of amyotrophic lateral sclerosis (ALS). We enrolled male subjects with SBMA (n = 40) and ALS (n = 25) along with 15 healthy control subjects, and assessed their respiratory function, motor function, and muscle strength. Predicted values of peak expiratory flow (%PEF) and forced vital capacity were decreased in subjects with SBMA compared with controls. In SBMA, both values were strongly correlated with the trunk subscores of the motor function tests and showed deterioration relative to disease duration. Compared with activities of daily living (ADL)-matched ALS subjects, %PEF, tongue pressure, and grip power were substantially decreased in subjects with SBMA. Both immunofluorescence and RT-PCR demonstrated a selective decrease in the expression levels of the genes encoding the myosin heavy chains specific to fast-twitch fibers in SBMA subjects. The mRNA levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha and peroxisome proliferator-activated receptor delta were up-regulated in SBMA compared with ALS and controls. In conclusion, %PEF is a disease-specific respiratory marker for the severity and progression of SBMA. Explosive muscle strength, including %PEF, was selectively affected in subjects with SBMA and was associated with activation of the mitochondrial biogenesis-related molecular pathway in skeletal muscles.