Investigation of MGF mRNA expression in patients with amyotrophic lateral sclerosis using parallel in vivo and in vitro approaches.
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.
Evans
Richard M
RM
Department of Clinical Neurosciences, UCL Institute of Neurology, London, UK.
Harridge
Stephen D R
SD
Velloso
Cristiana P
CP
Yang
Shi Yu
SY
Goldspink
Geoffrey
G
Orrell
Richard W
RW
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
D010455:Peptides; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I