This study shows that cotreatment with insulin-like growth factor-I (IGF-I) and glycosaminoglycans (GAGs) prevents the onset of neuromuscular deficit in the m/m mutant mouse. These mice show a mid-to-late-life onset of progressive paralysis of the hind limb, that is correlated with altered innervation and reduced nerve-evoked isometric twitch tension in the extensor digitorum longus (EDL) muscle. Almost 50% of EDL nerve endings are negative for antisynaptophysin staining, while retrograde labelling with beta-cholera-toxin coupled to type IV horseradish and quantitative histological analysis show a small loss of EDL and lumbar cord motor neurons. At 10 months of age also forelimb function evaluated as grip strength is significantly reduced. Animals treated either with glycosaminoglycans alone or with IGF-I alone at low and high doses showed only a partial improvement of their condition. However, cotreatment of m/m mice with IGF-I and GAGs fully prevented the neuromuscular abnormalities, the twitch tension loss, the motor neuron decrease and the reduction of forelimb grip strength.

Long-term neuroprotective effects of glycosaminoglycans-IGF-I cotreatment in the motor neuron degeneration (mnd) mutant mouse / A. Gorio, E. Germani, E. Lesma, G. Rossoni, E. Muller, A. Di Giulio. - In: EUROPEAN JOURNAL OF NEUROSCIENCE. - ISSN 0953-816X. - 11:10(1999), pp. 3395-3404. [10.1046/j.1460-9568.1999.00730.x]

Long-term neuroprotective effects of glycosaminoglycans-IGF-I cotreatment in the motor neuron degeneration (mnd) mutant mouse

A. Gorio;E. Lesma;G. Rossoni;E. Muller;A. Di Giulio
1999

Abstract

This study shows that cotreatment with insulin-like growth factor-I (IGF-I) and glycosaminoglycans (GAGs) prevents the onset of neuromuscular deficit in the m/m mutant mouse. These mice show a mid-to-late-life onset of progressive paralysis of the hind limb, that is correlated with altered innervation and reduced nerve-evoked isometric twitch tension in the extensor digitorum longus (EDL) muscle. Almost 50% of EDL nerve endings are negative for antisynaptophysin staining, while retrograde labelling with beta-cholera-toxin coupled to type IV horseradish and quantitative histological analysis show a small loss of EDL and lumbar cord motor neurons. At 10 months of age also forelimb function evaluated as grip strength is significantly reduced. Animals treated either with glycosaminoglycans alone or with IGF-I alone at low and high doses showed only a partial improvement of their condition. However, cotreatment of m/m mice with IGF-I and GAGs fully prevented the neuromuscular abnormalities, the twitch tension loss, the motor neuron decrease and the reduction of forelimb grip strength.
Dermatan sulphate; Heparin sulphate; Motor neuron loss; Muscle atrophy; Muscle denervation
Settore BIO/14 - Farmacologia
EUROPEAN JOURNAL OF NEUROSCIENCE
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/185335
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