Delayed changes in growth factor gene expression during slow remyelination in the CNS of aged rats.
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.
Hinks
G L
GL
Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, United Kingdom.
Franklin
R J
RJ
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
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