Fibroblast growth factor inhibitors another Remyelination cue

Epub: Mierzwa et al. FGF2 and FGFR1 Signaling Regulate Functional Recovery Following Cuprizone Demyelination Neurosci Lett. 2013. doi:pii: S0304-3940(13)00430-8. 10.1016/j.neulet.2013.05.010. 

In demyelinating diseases, such as multiple sclerosis, remyelination offers the potential to recover function of viable denuded axons by restoring saltatory conduction and/or protecting from further damage. Mice with genetic reduction of fibroblast growth factor 2 (Fgf2) or Fgf receptor 1 (Fgfr1) exhibit dramatically improved remyelination following experimental demyelination with cuprizone. The current studies are the first to test neurobehavioral outcomes with these gene deletions that improved remyelination. The cuprizone protocols used did not produce overt abnormalities but did reduce bilateral sensorimotor coordination (complex wheel task) and increase sociability (two chamber apparatus with novel mouse). A significant effect of genotype was observed on the complex wheel task but not in the sociability apparatus. Specifically, complex wheel velocities for Fgf2 nulls improved significantly after removal of cuprizone from the diet. This improvement in Fgf2 null mice occurred following either acute (6 wk) or chronic (12 wk) demyelination. Plp/CreERT:Fgfr1fl/fl mice administered tamoxifen at 10 wks of cuprizone treatment to induce Fgfr1 knockdown also showed improved recovery of running velocities on the complex wheels. Therefore, constitutive deletion of Fgf2 or Fgfr1 knockdown in oligodendrocyte lineage cells is sufficient to overcome impairment of sensorimotor coordination after cuprizone demyelination.
An FGF molecule


Fibroblast (connective tissue cell) growth factors make fibroblasts and other cells growth. This study indicates that inhibitors of fibroblast growth factor 2 (Fgf2) or Fgf receptor 1 (Fgfr1) could improve remyelination and this could be associated with functional changes. So yet more cues for remyelination. We need to know how many are the critical key regulators as it is clear to me there are now alot of factors that promote this activity. There is only one way to find out....lets to the the trials.

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