Fibroblast growth factor 2 (FGF2) and FGF receptor expression in an experimental demyelinating disease with extensive remyelination

Fibroblast growth factor 2 (FGF2) is an excellent candidate to regulate rem yelination based on its proposed actions in oligodendrocyte lineage cell de velopment in conjunction with its involvement in CNS regeneration. To asses s the potential for FGF2 to play a role in remyelination, we examined the e xpression pattern of FGF2 and FGF receptors (FGFRs) in an experimental demy elinating disease with extensive remyelination, Adult mice were intracrania lly injected with murine hepatitis virus strain A-59 (MHV-A59) to induce fo cally demyelinated spinal cord lesions that spontaneously remyelinate, with corresponding recovery of motor function. Using kinetic RT-PCR analysis of spinal cord RNA, we found significantly increased levels of FGF2 mRNA tran scripts, which peaked during the initial stage of remyelination. Analysis o f tissue sections demonstrated that increased levels of FGF2 mRNA and prote in were localized within demyelinated regions of white matter, including hi gh FGF2 expression associated with astrocytes, The expression of correspond ing FGF receptors was significantly increased in lesion areas during the in itial stage of remyelination. In normal and lesioned white matter, oligoden drocyte lineage cells, including progenitors and mature cells, were found t o express multiple FGFR types (FGFR1, FGFR2, and/or FGFR3), In addition, in lesion areas, astrocytes expressed FGFR1, FGFR2, and FGFR3. These findings indicate that, during remyelination, FGF2 may play a role in directly regu lating oligodendrocyte lineage cell responses and may also act through para crine or autocrine effects on astrocytes, which are known to synthesize oth er growth factors and immunoregulatory molecules that influence oligodendro cyte lineage cells. Published 2000 Wiley-Liss, Inc.(dagger).