title: Decreased Peak Expiratory Flow Associated with Muscle Fiber-Type Switching in Spinal and Bulbar Muscular Atrophy.
abstract: 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.
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: Atsushi
authors.initials: A
authors.lastname: Hashizume
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: Tomonori
authors.initials: T
authors.lastname: Inagaki
authors.affiliation: 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: Naohide
authors.initials: N
authors.lastname: Kondo
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Kawai
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: 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.
authors.forename: Haruki
authors.initials: H
authors.lastname: Koike
authors.affiliation: Neuroscience Program, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Katherine
authors.initials: K
authors.lastname: Halievski
authors.affiliation: Neuroscience Program, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Jordan
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.|Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000503:physiopathology; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology*; D053580:Muscle Strength; D009134:Muscular Atrophy, Spinal / Q000378:metabolism / Q000503:physiopathology*; D020966:Muscular Disorders, Atrophic / Q000378:metabolism / Q000503:physiopathology; D047494:PPAR delta / Q000378:metabolism; D010366:Peak Expiratory Flow Rate; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012129:Respiratory Function Tests
chemical_list: D047494:PPAR delta; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger