Article
Ablation of oligodendroglial FGFR1 results in enhanced Trk B expression in mice
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Authors
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Ranjithkumar Rajendran
- Justus Liebig University, Neurology, Gießen, Germany
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Mario Giraldo Velásquez
- Sozialstiftung Bamberg, Neurology, Bamberg, Germany
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Martin Berghoff
- Justus Liebig University, Neurology, Gießen, Germany
| Published: | August 25, 2015 |
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Outline
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Introduction: Fibroblast growth factors and its receptors play an important role in proliferation, differentiation and survival of oligodendrocytes and neurons in the CNS. Fibroblast growth factor receptor 1 (FGFR1) signaling includes RAS-RAF-MAPK and PI3K-AKT pathways. In a model of toxic demyelination, conditional FGFR1 deletion in oligodendrocytes resulted in increased remyelination and axonal density suggesting that oligodendroglial FGFR1 negatively regulate the axonal pathology. It remains unclear though how oligodendroglial FGFR1 regulates axonal density. Signals include BDNF, NGF and neurotrophin from glial cells enhances the neuronal cell density through promoting neuronal cell growth.
Objectives: The objective of this study was to characterize how oligodendroglial Fgfr1 modulates axonal density.
Materials and methods: Four-week-old female B6.Cg-Tg(PLP1-cre/ERT)3Pop Fgfr1tm5.1Sor mice were injected with Tamoxifen (Fgfr1ind-/-) or vehicle (control) for 5 consecutive days, spinal cord and cortex tissue were collected fifteen days later. Olig2(+) and NogoA(+) oligodendrocyte population was analyzed by IHC. TrkB expression, ERK and AKT phosphorylation was analyzed by western blot.
Results: Fgfr1 deletion does not alter the number of Olig2(+) and NogoA(+) oligodendrocytes. In the spinal cord both ERK (p=0.029) and AKT (p=0.045) phosphorylation was increased in Fgfr1ind-/- mice compared to controls. In the cortex phosphorylation of ERK and AKT was not different between Fgfr1ind-/- mice and controls. In Fgfr1ind-/- mice increased expression of TrkB was observed in the cortex (p≤0.05), there was a strong trend towards an increase of TrkB in the spinal cord (p=0.073).
Conclusions: FGFR1 deletion in oligodendrocytes is associated with an increase of TrkB receptor, which binds BDNF. BDNF is known to enhance axonal density. The exact underlying mechanisms, which connect FGFR1 and TrkB remain unclear. Possibly the intracellular signaling ERK and AKT phosphorylation is involving. Differences between spinal cord and cortex may be due to the differences in oligodendrocyte density and Fgfr1 expression.
