|Department:||FB 08 - Biologie und Chemie|
|Full text PDF:||http://geb.uni-giessen.de/geb/volltexte/2015/11358|
Fibroblast growth factors (FGFs) exert diverse biological effects by binding and activation of specific fibroblast growth factor receptors (FGFRs). Recent studies on the function of FGF2 in MOG35-55-induced experimental autoimmune encephalitis (EAE) showed that systemic deletion of FGF2 leads to a more severe disease course, increased lymphocyte and macrophage infiltration and decreased remyelination. In the present study the in vivo function of the corresponding receptor Fgfr1 was characterized using an oligodendrocyte-specific genetic approach. Plp/CreERT:Fgfr1fl/fl mice were administered tamoxifen to induce conditional Fgfr1 deletion in oligodendrocytes (referred to as Fgfr1ind-/-). In MOG35-55-induced EAE the Fgfr1ind-/- mice show a delayed onset of disease, less maximum disease severity and enhanced recovery. Decreased lymphocyte and macrophage/microglia infiltration, and myelin and axon degeneration are found in Fgfr1ind-/- mice. In acute EAE downregulation of proinflammatory cytokines such as TNF-alpha, IL-1beta and IL-6, in chronic EAE downregulation of the CX3CL1/CX3CR1 pathway is seen in Fgfr1ind-/- mice. Furthermore, increased expression of BDNF, TrkB (neurotrophic tyrosine kinase receptor, type 2) and decreased expression of Lingo-1 are found in Fgfr1ind-/- mice. Fgfr1 ablation in oligodendrocytes showed increased TrkB expression in whole lysate of cortex and spinal cord. These data suggest that impaired signalling via oligodendroglial Fgfr1 has a beneficial effect on MOG35-55-induced EAE. These findings on the oligodendroglial Fgfr1 pathway may offer a new target for developing therapy in multiple sclerosis.