title: Granulocyte Colony-Stimulating Factor Ameliorates Skeletal Muscle Dysfunction in Amyotrophic Lateral Sclerosis Mice and Improves Proliferation of SOD1-G93A Myoblasts in vitro.
abstract: Amyotrophic lateral sclerosis (ALS) causes loss of upper and lower motor neurons as well as skeletal muscle (SKM) dysfunction and atrophy. SKM is one of the tissues involved in the development of ALS pathology, and studies in a SOD1-G93A mouse model of ALS have demonstrated alterations in SKM degeneration/regeneration marker expression in vivo and defective mutant myoblast proliferation in vitro. Granulocyte colony-stimulating factor (G-CSF) has been shown to alleviate SOD1-G93A pathology. However, it is unknown whether G-CSF may have a direct effect on SKM or derived myoblasts.
  
  
  
  To investigate effects of G-CSF and its analog pegfilgrastim (PEGF) on SOD1-G93A- associated SKM markers in vivo and those of G-CSF on myoblast proliferation in vitro.
  
  
  
  The effect of PEGF treatment on hematopoietic stem cell mobilization, survival, and motor function was determined. RNA expression of SKM markers associated with mutant SOD1 expression was quantified in response to PEGF treatment in vivo, and the effect of G-CSF on the proliferation of myoblasts derived from mutant and control muscles was determined in vitro.
  
  
  
  Positive effects of PEGF on hematopoietic stem cell mobilization, survival, and functional assays in SOD1-G93A animals were confirmed. In vivo PEGF treatment augmented the expression of its receptor Csf3r and alleviated typical markers for mutant SOD1 muscle. Additionally, G-CSF was found to directly increase the proliferation of SOD1-G93A, but not wild-type primary myoblasts in vitro.
  
  
  
  Our results support the beneficial role of the G-CSF analog PEGF in a SOD1-G93A model of ALS. Thus, G-CSF and its analogs may be directly beneficial in diseases where the SKM function is compromised.
authors.affiliation: LAGENBIO, Facultad de Veterinaria, Instituto Agroalimentario de Aragón (IA2), Universidad de Zaragoza-CITA, and IIS Aragón, Zaragoza, Spain.
authors.forename: Amaya
authors.initials: A
authors.lastname: Rando
authors.forename: Samanta
authors.initials: S
authors.lastname: Gasco
authors.forename: Miriam
authors.initials: M
authors.lastname: de la Torre
authors.forename: Alberto
authors.initials: A
authors.lastname: García-Redondo
authors.forename: Pilar
authors.initials: P
authors.lastname: Zaragoza
authors.forename: Janne M
authors.initials: JM
authors.lastname: Toivonen
authors.forename: Rosario
authors.initials: R
authors.lastname: Osta
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009465:Neuromuscular Agents / Q000494:pharmacology*; D011092:Polyethylene Glycols; D011994:Recombinant Proteins / Q000494:pharmacology; D000072105:Superoxide Dismutase-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D009465:Neuromuscular Agents; D011994:Recombinant Proteins; C000606290:SOD1 protein, human; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000072105:Superoxide Dismutase-1; D000069585:Filgrastim