title: Systemic administration of insulin-like growth factor decreases motor neuron cell death and promotes muscle reinnervation.
abstract: Neonatal sciatic nerve axotomy causes motoneuron death and muscle denervation atrophy. The aim of the present study was to determine whether insulin-like growth factor-I (IGF-I) administration promotes muscle reinnervation and counteracts motor neuron loss after such an injury. Six weeks after sciatic nerve axotomy performed in 2-day-old pups, the number of motor neurons, as assessed by retrograde transport of horseradish peroxidase injected into the extensor digitorum longus (EDL) muscle, was reduced from 52 +/- 3 to 26 +/- 3. Subsequent administration of IGF-I at the doses of 0.02 mg/kg or 1 mg/kg increased the number of motor neurons to 35 +/- 2 and 37 +/- 5, respectively. The effect on motoneuron survival was accompanied by improved muscle fibre morphometry and restoration of indirect EDL muscle isometric twitch tension, which was about 80 % of control values for both doses of IGF-I compared with 60% observed with saline treatment. Reinnervated EDL muscle from saline-treated rats cannot hold tetanic tension, which is, however, achieved after IGF-I treatment at either dose. Thus, both high and low doses of IGF-I counteracted motoneuron death and improved muscle reinnervation following neonatal sciatic nerve axotomy. IGF-I at 5 microg/kg failed to increase muscle reinnervation.
authors.affiliation: Laboratory for Research on Pharmacology of Neurodegenerative Disorders, University of Milan, Milano, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Vergani
authors.forename: A M
authors.initials: AM
authors.lastname: Di Giulio
authors.forename: M
authors.initials: M
authors.lastname: Losa
authors.forename: G
authors.initials: G
authors.lastname: Rossoni
authors.forename: E E
authors.initials: EE
authors.lastname: Muller
authors.forename: A
authors.initials: A
authors.lastname: Gorio
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology*; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation*; D009133:Muscular Atrophy / Q000209:etiology; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007334:Insulin-Like Growth Factor I