Systemic administration of insulin-like growth factor decreases motor neuron cell death and promotes muscle reinnervation

✍ Scribed by Letizia Vergani; Anna Maria Di Giulio; Matteo Losa; Giuseppe Rossoni; Eugenio E. Muller; Alfredo Gorio

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 119 KB
• Volume: 54
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(19981215)54:6<840::aid-jnr12>3.0.co;2-l

✦ Synopsis

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 µg/kg failed to increase muscle reinnervation.