title: Investigation of MGF mRNA expression in patients with amyotrophic lateral sclerosis using parallel in vivo and in vitro approaches.
abstract: In an animal model of ALS, intramuscular administration of MGF, the IGF-I Ec gene splice variant, improved muscle strength and increased both motor unit and motor neuron survival. Here we investigated whether there is a deficit in MGF production in the muscles of patients with ALS. We used complementary in vivo and in vitro techniques to study the IGF-I splice variant response of human muscle to exercise or mechanical stretch. We assessed the levels of MGF and IGF-IEa mRNA in muscle biopsy samples from healthy subjects and patients with ALS, before and after exercise. We used primary muscle cells to build three-dimensional collagen constructs and subjected them to a ramp stretch. Patients with ALS had similar baseline levels of MGF and IGF-IEa mRNA to healthy controls. No up-regulation was seen in either group within a short time of a single bout of low intensity exercise. Three-dimensional human muscle constructs also detected no response to a mechanical stretch from either control subjects or ALS. We conclude that the pathology of ALS does not include a deficit in baseline levels of MGF and IGF-IEa mRNA splice variants in muscle.
authors: Department of Clinical Neurosciences, UCL Institute of Neurology, London, UK.
authors: Richard M
authors: RM
authors: Evans
authors: Stephen D R
authors: SD
authors: Harridge
authors: Cristiana P
authors: CP
authors: Velloso
authors: Shi Yu
authors: SY
authors: Yang
authors: Geoffrey
authors: G
authors: Goldspink
authors: Richard W
authors: RW
authors: Orrell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing / Q000235:genetics*; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D001706:Biopsy; D015444:Exercise / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology; D032446:Myoblasts / Q000473:pathology / Q000502:physiology; D010455:Peptides / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D055815:Young Adult
chemical_list: D010455:Peptides; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I