STABILIZING NEUROMUSCULAR CONTACTS INCREASES MOTONEURON SURVIVAL AFTER NEONATAL NERVE INJURY IN RATS

Following sciatic nerve crush at birth the rat soleus muscle is render ed permanently weak. This reduction in muscle force is caused by the l oss of a proportion of its motoneurons. Furthermore, motoneurons that survive and reach the muscle fail to reoccupy a sufficient number of d enervated muscle fibres to compensate for the loss of neurons. Both th e loss of motoneurons and poor reinnervation may be due to the inabili ty of the regenerating axons to establish and maintain neuromuscular c ontacts. Application of leupeptin, an inhibitor of a calcium-activated neutral protease and some serine proteases, is known to help in the m aintenance of neuromuscular contacts during development and axonal spr outing. Here we examined whether protecting new neuromuscular contacts formed between regenerating axons and denervated muscle fibres after nerve injury, would influence the survival of motoneurons and improve muscle recovery. This study shows that in muscles treated with leupept in the reduction in weight and force output after nerve crush at birth was significantly less than in those that were untreated. Moreover, t he number of motor units in the leupeptin-treated muscles was signific antly higher than in untreated muscles. Thus, treating regenerating ne rve terminals with leupeptin during early stages of reinnervation resc ues motoneurons and improves muscle recovery.