Inhibition of Myelin Formation by Astrogliosis

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Long-term cultured astrocytes of newborn ICR mice maintained for more than 12 weeks without cell passage became fibrous and hypertrophic, and exhibited intense immunostaining with anti-GFAP antibodies, characteristics analogous to gliotic astrocytes. In newborn mouse cerebellar tissue explanted on these astrocytes myelination was completely inhibited, while in that explanted on astrocytes maintained for less than 3 weeks myelination occurred vigorously. Culture medium containing 80% or more conditioned medium of longterm cultured astrocytes significantly inhibited myelin formation in cerebellar tissues explanted in collagen-coated 24-well plates, compared with that containing conditioned medium of astrocytes maintained for less than 3 weeks. These findings indicate that gliotic astrocytes produce myelination inhibition factor (s) which may partly explain the poor remyelination in chronic demyelination plaques of multiple sclerosis. Next, we searched for gliosis related genes by differential display method. We obtained a gene named OASIS which is strongly induced in the long-term cultured astrocytes. The OASIS gene encoded a putative transcription factor belonging to CREB/ATF gene family. The expression of the OASIS mRNA was induced in the mouse cerebral cortex in response to cryo-injury. The distribution pattern of the OASIS-positive cells was very similar to that of the GEAP-positive cells. These results support that long-term cultured astrocytes is a good model for gliosis in vitro, and suggest that OASIS plays a role for gliosis.