Evaluation of the Fibroblast Growth Factor Receptor 2 (FGFR2) in Experimental Autoimmune Encephalomyelitis (EAE) and its Possible Role in Multiple Sclerosis (MS)

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KamaliSalar_2016_04_06.pdf (7.8 MB)

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2016

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http://dx.doi.org/10.22029/jlupub-14283

Abstract

Myelin is a bioactive membrane established by oligodendrocytes during postnatal development and is essential for receiving and conducting electrical impulses by axons. Myelin acts as a target during many autoimmune neurological conditions such as MS. FGF signaling is known to be crucial for development, proliferation and maintenance of oligodendrocytes and OPCs, hence, influencing myelination. Yet, the role of FGFR signaling in MS and EAE is poorly understood. Hypothesizing MOG35-55-EAE will cause more severe symptoms in oligodendroglial Fgfr2 depleted mice, we designed a Tamoxifen inducible PLP Cre mediated conditional Fgfr2 knockout in oligodendrocyte passage under C57BL/6 background. No phenotypic changes were observed in Fgfr2ind-/- mice. To our surprise, Fgfr2ind-/- showed a milder disease course of MOG35-55-EAE coupled with reduced immune infiltration (T-cells, B-cells, macrophages/ microglia), reduced demyelination, less inflammation, and better axonal preservation. Ablation of Fgfr2 in oligodendrocytes caused reduced ERK phosphorylation as well as increased TrkB expression and AKT phosphorylation. The number of OLs and OPCs were not altered in Fgfr2ind-/- mice in EAE induced or non-EAE condition when compared to their respective controls. Prevention regimen of GA treatment delayed and further ameliorated the MOG35-55-EAE manifestation in Fgfr2ind-/- mice. Taken together, our findings indicate a deteriorating role for FGFR2 in the pathology of MOG35-55-EAE by boosting immune response through MEK/ERK, PI13/AKT, and TrkB crosstalk and signaling. Therefore, FGFR2 and its downstream signaling mediators could serve as effective potential treatment prospects in tackling immunological related CNS disorders.

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