Rescue of injured adult motoneurones with the gene for a splice variant of IGF-1 (MGF) isolated from skeletal muscle

We have compared the neuroprotective effects of the liver type isoform of insulin-like growth factor-1 (L.IGF-1) with an IGF-1 splice variant (MGF) isolated from active muscle (Yang et al 1996 J. Muscle Cell Res. Cell Motil. 4:487-496). The right snout muscle of groups of 4-6 anaesthetised adult rats was injected with plasmid DNA containing rat genes for either IGF-1 or MGF. Both genes were under the control of a cytomegalovirus promoter and a myosin light chain enhancer. Seven days later, the right facial nerve was avulsed. One month after avulsion, total numbers of facial motoneurones were determined bilaterally using an optical fractionator method. Non-operated rats had approximately 3,400 motoneurones in the facial nucleus. One month following nerve avulsion, non-injected rats and those injected with vector only, showed a 75% reduction of motoneurone number ipsilaterally. Prior intramuscular injection of vector containing L.IGF-1 or MGF genes reduced this loss at 1 month to 53% and 21%, respectively. Neuroprotection was not confined to the motoneurone pools innervating the snout muscles. The results indicate that MGF is twice as potent as the commonly-used liver isoform of IGF-1 for the prevention of adult motoneuronal loss.