Delayed changes in growth factor gene expression during slow remyelinationin 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 expressi on 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, TG F-beta1, and PDGF-A mRNA expression during remyelination of lysolecithin-in duced demyelination in the spinal cord of young adult and old adult rats. I GF-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 exp ression was delayed in old rats compared to young rats, but after 5 days bo th age groups had similar patterns of expression, as was the expression pat tern of FGF-P mRNA at all survival times. In neither age group were increas es in CNTF, NT-3, or GGF-2 mRNA expression detected. An analysis of the mac rophage response using oligonucleotide probes for scavenger receptor-a mRNA indicated that differences in the macrophage response in young and old ani mals was the likely cause of the age related change in IGF-I and TGF-beta1 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 oligodendro cyte progenitor recruitment, while IGF-I and TGF-beta1 trigger the differen tiation of the recruited cells into myelinating oligodendrocytes.