| dc.description | The expression of myelin-specific genes was investigated in two models of peripheral neuropathy. The distal segment of the crush-injured rat sciatic nerve presents an opportunity to study molecular events during transient degeneration and subsequent remyelination. The distal segment of the permanently transected nerve is however incapable of remyelination in the absence of Schwann cell-axonal contact. The temporal course of expression of the genes encoding the major peripheral nervous system (PNS) myelin-specific proteins PO (the major PNS myelin glycoprotein), the myelin basic proteins (MBP) and the myelin-associated glycoprotein (MAG) suggested that PO and MBP genes are co-regulated in the peripheral nerve, and their expression is induced 10 to 14 days post crush-injury. The MAG gene is regulated in a different manner, and may be induced prior to the major myelin genes during remyelination. In contrast, the gene encoding the myelin enzyme 2$\sp\prime$,3$\sp\prime$-cyclic nucleotide 3$\sp\prime$-phosphodiesterase (CNPase) was induced over adult levels in the period following crush-injury as well as after permanent transection. The expression of the CNS myelin proteolipid protein (PLP) gene in the developing, degenerating and regenerating PNS was also examined and compared to that of other peripheral nerve myelin-specific or myelin-associated genes. PLP gene expression in the peripheral nerve remains relatively dissociated from axonal influences. The effect of a permanent transection on a crushed, regenerating sciatic nerve was also evaluated to establish the degree of axonal control exerted upon Schwann cells that were previously induced to remyelinate. The induction of myelin gene expression observed during peripheral nerve regeneration is dependent on continuous signals from the ingrowing axons. The crush-transected model permits the classification of myelin genes, according to their response to Schwann cell-axonal contact. PO and MBP genes appear to be co-regulated and are expressed at basal levels in the absence of axonal contact. Levels of MAG encoding transcripts were reduced to undetectable levels after transection and after crush-transection, suggesting that the MAG gene is stringently controlled by signals emanating from the axon. CNPase coding transcripts, in contrast, were induced to higher than normal levels after all forms of nerve injury, although CNPase enzyme activities followed the pattern of demyelination and remyelination in these experimental models. The PLP gene was also atypical, in that its expression appeared to be relatively independent of axonal control. These results demonstrate the presence of diverse modes of regulation of myelin genes at the levels of transcription, post-transcription, translation, and post-translation. They are consistent with the concept that both remyelination and myelination during neural development are cellular processes under hierarchical control. | en_US |
