Distinctive patterns of PDGF-A, FGF-2, IGF-I, and TGF-beta 1 gene expression during remyelination of experimentally-induced spinal cord demyelination

Although remyelination is a well-recognized regenerative process following both experimental and naturally occurring CNS demyelination, remarkably lit tle is known about the molecules involved in its orchestration. in this stu dy we have examined the mRNA expression of seven growth factors that influe nce oligodendrocyte lineage cells, during the remyelination of lysolecithin -induced demyelination in the rat spinal cord. These lesions involve rapid demyelination of axons, which undergo extensive remyelination between 10 an d 28 days. The distribution and levels of expression of PDGF-A, IGF-1, CNTF , FGF-2, TGF-beta 1, GGF-2, and NT-3 mRNAs were examined at 2, 5, 7, 10, 14 , 21, and 28 days post-lesion induction, both within the lesion and within dorsal root ganglia whose axons traverse the lesion, by quantitative in sit u hybridization using S-35-labeled oligonucleotide probes. Large increases in IGF-1 and TGF-beta 1 mRNAs were evident within the spinal cord by 5 days . These levels peaked at 10 days at a time when new myelin sheaths appear a nd had declined by 28 days. Increases in FGF-2 and PDGF-A mRNAs were less i ntense and less widely distributed than those of IGF-1 and TGF-beta 1, but remained elevated for a longer duration. There were no changes in expressio n of CNTF, NT-3, or GGF-2 mRNAs within the lesioned cords; neither were the re changes in levers of expression of any growth factor mRNAs in the dorsal root ganglia. This work therefore indicates that some but not all members of the family of growth factors that affect the oligodendrocyte lineage are expressed during remyelination of demyelinated spinal cord axons and provi des the data on which future studies on the specific roles of these factors in orchestrating this important regenerative process will be based.