Distinctive patterns of PDGF-A, FGF-2, IGF-I, and TGF-beta1 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 little is known about the molecules involved in its orchestration. In this study we have examined the mRNA expression of seven growth factors that influence 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 and 28 days. The distribution and levels of expression of PDGF-A, IGF-I, CNTF, FGF-2, TGF-beta1, 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 transverse the lesion, by quantitative in situ hybridization using 35S-labeled oligonucleotide probes. large increases in IGF-I and TGF-beta1 mRNAs were evident within the spinal cord by 5 days. These levels peaked at 10 days at a time when new myelin sheaths appear and had declined by 28 days. Increases in FGF-2 and PDGF-A mRNAs were less intense and less widely distributed than those of IGF-I and TGF-1, but remained elevated for a longer duration. There were no changes in expression of CNTF, NT-3, or GGF-2 mRNAs within the lesioned cords; neither were ther changes in levels 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 provides the data on which future studies on the specific roles of these factors in orchestrating this important regenerative process will be based.
Hinks
G L
GL
Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 OES, United Kingdom.
Franklin
R J
RJ
D000818:Animals; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008244:Lysophosphatidylcholines / Q000633:toxicity; D009186:Myelin Sheath / Q000187:drug effects / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology*; D015345:Oligonucleotide Probes; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics*
D008244:Lysophosphatidylcholines; D015345:Oligonucleotide Probes; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I