Knock Out Of Oligodendroglial Fgfr1 Causes Increased Trkb Receptor Expression In C57b1/6 Mice

Objective:The objective of this study was to evaluate the effect of oligodendroglial Fgfr1 on TrkB expression in C57Bl/6 mice.Background:FGF mediate diverse biological effects including proliferation, differentiation and migration of cells by binding to FGF receptors (FGFRs). In vivo knock out of oligodendroglial Fgfr1 resulted in enhanced axonal protection in the CNS. TrkB is the receptor for BDNF, a substance known to protect axons and to promote neuronal growth. An in vitro study suggested that FGF may also bind to TrkB. We hypothesized that knock out of oligodendroglial Fgfr1 would result in activation of TrkB receptor expression by FGF.Design/Methods:Tamoxifen injectable PLP-Cre-mediated deletion of Fgfr1 in oligodendrocytes was done in four-week-old female Plp1-cre:Fgfr1fl/fl mice (Fgfr1ind-/- mice). Fifteen days later spinal cord, cortex, brain stem and cerebellum tissues were analyzed for TrkB expression. Oligodendrocyte population and Fgfr1 downstream signaling were analyzed by IHC/Westernblot.Results:Fgfr1ind-/- mice showed increased expression of TrkB in the cortex (P ≤ 0.05) and spinal cord (P = 0.073), and reduced TrkB expression in the brain stem (P ≤ 0.0001). Oligodendrocyte populations in the spinal cord were not different between Fgfr1ind-/- mice and controls. There was increased expression of ERK and AKT phosphorylation in the spinal cord of Fgfr1ind-/- mice (pERK: P = 0.029, pAKT: P = 0.045) but not in the cortex.Conclusions:Knock out of oligodendroglial Fgfr1 may enhance neuroprotection through increased TrkB receptor expression. Increased TrkB expression is associated with increased ERK and AKT phosphorylation. Knock out of oligodendroglial Fgfr1 does not alter the oligodendrocyte populations. Disclosure: Dr. Rajendran has nothing to disclose. Dr. Velasquez has nothing to disclose. Dr. Berghoff has received personal compensation for activities with Bayer Vital, Merck Serono, Teva, Biogen Idec, and Novartis as a speaker.