CNTF is up‐regulated in astrocytes during spinal cord remyelination and stimulates FGF‐2 production

FGF‐2 is a potent mitogen and survival factor for oligodendrocyte progenitors in vitro, and it is induced in astrocytes in conjunction with successful remyelination during recovery from murine hepatitis virus (MHV) induced spinal cord demyelination. However, the factor(s) responsible for inducing FGF‐2 after demyelination in astrocytes are unknown. Here we used in vivo and in vitro paradigms to assess whether ciliary neurotrophic factor (CNTF) could be responsible for FGF‐2 induction during remyelination. In mice recovering from MHV‐induced demyelination, increased CNTF expression coincided with spinal cord remyelination. Immunohistochemistry demonstrated that CNTF protein was present within astrocytes surrounding and within remyelinating lesions. After directly injecting CNTF into the spinal cord, FGF‐2 mRNA increased in spinal cord astrocytes. Furthermore, CNTF induced FGF‐2 mRNA over 2.5 fold in cultured mouse spinal cord astrocytes as determined by kinetic RT–PCR analysis. Although IL‐1β has been implicated in FGF‐2 production, IL‐1β mRNA was not detected during remyelination, nor did IL‐1β induce FGF‐2 mRNA from mouse spinal cord astrocytes in vitro. Altogether, these results strongly implicate CNTF as an upstream positive regulator of FGF‐2 production in astrocytes during early remyelination. Acknowledgements: Supported by NMSS Award #RG 3837 (SWL) and NS 33316 (RCA).