Fibroblast growth factor-2 inhibits myelin production by oligodendrocytes in vivo

Fibroblast growth factor-2 (FGF-2) controls in part the timely differentiat ion of oligodendrocytes into the myelin-producing cells of the CNS. However , although differentiated oligodendrocytes express FGF receptors (R), the e ffect of FGF-2 on myelin-producing oligodendrocytes in vivo was unknown. In the present study, we show that delivery of FGF-2 into the cerebrospinal f luid of anaesthetized rat pups, aged postnatal day (P) 6 to 9, induced a se vere loss of myelin in the caudal anterior medullary velum (AMV). Furthermo re, we show that the caudal AMV was myelinated at the time of treatment, so the effects of FGF-2 represent a loss of myelin and not delayed differenti ation. This was confirmed by injection of platelet-derived growth factor-AA (PDGF-AA), a factor known to affect the differentiation of PDGF-alphaR exp ressing oligodendrocyte progenitors, but which did not induce myelin loss i n the caudal AMV and did not affect differentiated oligodendrocytes, which do not express PDGF-alphaR. Compared to controls treated with saline or PDG F-AA, FGF-2 induced an accumulation of PLP protein and MBP mRNA within the somata of myelin-producing oligodendrocytes. The results indicate that FGF receptor signalling disrupts myelin production in differentiated oligodendr ocytes; in vivo and interrupted the transport of myelin-related gene produc ts from the oligodendrocyte cell body to their myelin sheaths.