Oligodendroglial fibroblast growth factor receptor 1 gene targeting protects mice from experimental autoimmune encephalomyelitis through ERK/AKT phosphorylation.

Fibroblast growth factors (FGFs) exert diverse biological effects by binding and activation of specific fibroblast growth factor receptors (FGFRs). FGFs and FGFRs have been implicated in demyelinating pathologies including multiple sclerosis. In vitro activation of the FGF2/FGFR1 pathway results in downregulation of myelin proteins. FGF1, 2 and 9 have been shown to be involved in the pathology of multiple sclerosis. Recent studies on the function of oligodendroglial FGFR1 in a model of toxic demyelination showed that deletion of FGFR1 led to increased remyelination and preservation of axonal density and an increased number of mature oligodendrocytes. In the present study the in vivo function of oligodendroglial FGFR1 was characterized using an oligodendrocyte-specific genetic approach in the most frequently used model of multiple sclerosis the MOG35-55 -induced EAE. Oligodendroglial FGFR1 deficient mice (referred to as Fgfr1ind-/- ) showed a significantly ameliorated disease course in MOG35-55 -induced EAE. Less myelin and axonal loss, and reduced lymphocyte and macrophage/microglia infiltration were found in Fgfr1ind-/- mice. The reduction in disease severity in Fgfr1ind-/- mice was accompanied by ERK/AKT phosphorylation, and increased expression of BDNF and TrkB. Reduced proinflammatory cytokine and chemokine expression was seen in Fgfr1ind-/- mice compared with control mice. Considering that FGFR inhibitors are used in cancer trials, the oligodendroglial FGFR1 pathway may provide a new target for therapy in multiple sclerosis.