title: Delayed changes in growth factor gene expression during slow remyelination in the CNS of aged rats.
abstract: In this study we have examined whether the slower rate of CNS remyelination that occurs with age is associated with a change in growth factor expression patterns, an association that would provide further support for a causal relationship between growth factors and remyelination. Using quantitative in situ hybridization we have shown that there are differences in IGF-I, TGF-beta 1, and PDGF-A mRNA expression during remyelination of lysolecithin-induced demyelination in the spinal cord of young adult and old adult rats. IGF-I and TGF-beta1 mRNA expression in old rats had a delayed and lower peak expression compared to young rats. The initial increase in PDGF-A mRNA expression was delayed in old rats compared to young rats, but after 5 days both age groups had similar patterns of expression, as was the expression pattern of FGF-2 mRNA at all survival times. In neither age group were increases in CNTF, NT-3, or GGF-2 mRNA expression detected. An analysis of the macrophage response using oligonucleotide probes for scavenger receptor-B mRNA indicated that differences in the macrophage response in young and old animals was the likely cause of the age related change in IGF-I and TGF-beta 1 mRNA expression patterns. On the basis of these data we suggest a model of remyelination in which PDGF is involved in the initial phase of oligodendrocyte progenitor recruitment, while IGF-I and TGF-beta 1 trigger the differentiation of the recruited cells into myelinating oligodendrocytes.
authors.affiliation: Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, United Kingdom.
authors.forename: G L
authors.initials: GL
authors.lastname: Hinks
authors.forename: R J
authors.initials: RJ
authors.lastname: Franklin
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D018955:CD36 Antigens / Q000235:genetics; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006133:Growth Substances / Q000235:genetics*; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008244:Lysophosphatidylcholines; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009186:Myelin Sheath / Q000502:physiology*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000503:physiopathology; D009416:Nerve Regeneration / Q000502:physiology*; D015345:Oligonucleotide Probes; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013116:Spinal Cord / Q000254:growth & development / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1
chemical_list: D018955:CD36 Antigens; D005904:Glial Fibrillary Acidic Protein; D006133:Growth Substances; D008244:Lysophosphatidylcholines; D008565:Membrane Proteins; D015345:Oligonucleotide Probes; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C508961:Tgfb1 protein, mouse; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I