title: Exercise training reverses skeletal muscle atrophy in an experimental model of VCP disease.
abstract: BACKGROUND
  The therapeutic effects of exercise resistance and endurance training in the alleviation of muscle hypertrophy/atrophy should be considered in the management of patients with advanced neuromuscular diseases. Patients with progressive neuromuscular diseases often experience muscle weakness, which negatively impact independence and quality of life levels. Mutations in the valosin containing protein (VCP) gene lead to Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD) and more recently affect 2% of amyotrophic lateral sclerosis (ALS)-diagnosed cases.
  
  
  RESULTS
  The present investigation was undertaken to examine the effects of uphill and downhill exercise training on muscle histopathology and the autophagy cascade in an experimental VCP mouse model carrying the R155H mutation. Progressive uphill exercise in VCP(R155H/+) mice revealed significant improvement in muscle strength and performance by grip strength and Rotarod analyses when compared to the sedentary mice. In contrast, mice exercised to run downhill did not show any significant improvement. Histologically, the uphill exercised VCP(R155H/+) mice displayed an improvement in muscle atrophy, and decreased expression levels of ubiquitin, P62/SQSTM1, LC3I/II, and TDP-43 autophagy markers, suggesting an alleviation of disease-induced myopathy phenotypes. There was also an improvement in the Paget-like phenotype.
  
  
  CONCLUSIONS
  Collectively, our data highlights that uphill exercise training in VCP(R155H/+) mice did not have any detrimental value to the function of muscle, and may offer effective therapeutic options for patients with VCP-associated diseases.
authors.affiliation: Department of Pediatrics, Division of Genetics and Metabolism, University of California Irvine, Irvine, California, United States of America.
authors.forename: Angèle
authors.initials: A
authors.lastname: Nalbandian
authors.forename: Christopher
authors.initials: C
authors.lastname: Nguyen
authors.forename: Veeral
authors.initials: V
authors.lastname: Katheria
authors.forename: Katrina J
authors.initials: KJ
authors.lastname: Llewellyn
authors.forename: Mallikarjun
authors.initials: M
authors.lastname: Badadani
authors.forename: Vincent
authors.initials: V
authors.lastname: Caiozzo
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Kimonis
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D018797:Cell Cycle Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D051379:Mice; D008928:Mitochondria / Q000201:enzymology; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009154:Mutation; D010641:Phenotype; D010805:Physical Conditioning, Animal; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; D000074405:Valosin Containing Protein; C000614179:Vcp protein, mouse