Time-dependent alteration of insulin-like growth factor gene expression during nerve regeneration in regions of muscle enriched with neuromuscular junctions.

Insulin-like growth factors (IGFs) increase the rate of motor axon elongation, prevent motoneuron death, and may support the reestablishment of synapses following nerve injury. In situ hybridization was used in the present study to examine the temporal and spatial distribution of IGF gene expression in soleus muscle following sciatic nerve crush in rats. In intact muscle, IGF-II gene expression was generally low, and localized to interstitial cells, possibly fibroblast and Schwann cells. These cells were found in the middle of muscle which is enriched in neuromuscular junctions. IGF-II gene expression, 4-6 days postcrush, was increased in interstitial cells. Thereafter, IGF-II gene expression was also increased in muscle cells or cells closely associated with muscle fibers, such as satellite cells. IGF-II gene expression was increased to a much greater extent in the midregion of muscle enriched in end-plates than in the two ends of muscle, but returned towards normal following the reestablishment of functional synapses. On the other hand, IGF-I gene expression was only slightly increased following nerve crush, and this increase was associated with interstitial, but not muscle cells. These results show that the IGF-I and IGF-II genes are regulated by independent signals and may play separate roles during nerve regeneration. For example, a regional increase in IGF-II gene expression may support preferential nerve terminal sprouting in the middle of muscle enriched in neuromuscular junctions, thereby increasing the probability for the reestablishment of synapses.