Abstract Details

Title Oligodendroglial Specific Deletion of FGFR1 Protects Myelin in C57BL/6 Mice

Topic Multiple Sclerosis

Presentation(s) P3 - Poster Session 3 (12:00 PM-1:00 PM)

Poster/Presentation
Number 9-013

Objective

The objective of the study was to find the impact of FGFR1 ablation on myelin.

Background Fibroblast growth factors and their receptors play an important role in oligodendroglial proliferation, migration and differentiation. Fibroblast growth factor receptor 1 (FGFR1) is majorly expressed in the CNS and is increased in MS and experimental autoimmune encephalomyelitis (EAE).

Design/Methods Oligodendroglial FGFR1 conditional knockout mice were generated by crossing FGFR1 lox and Plp cre mice. Deletion of FGFR1 in oligodendrocytes was done in four-week-old female mice by i.p. injection of 100 µl Tamoxifen for 5 consecutive days (Fgfr1^ind-/- mice). Spinal cord tissues were collected from Fgfr1^ind-/- mice and controls on day 105 for analysis. The FGFR downstream signal molecules ERK, Akt, BDNF and TrkB were analyzed by western blot. Gene expression of TGFβ and LINGO-1 were analyzed by real time PCR.

Results On day 105 Fgfr1^ind-/-mice showed a downregulation of FGFR1, FGFR2, FGF2, pERK, CD200 and CNPase (p ≤ 0.05). There was no effect on BDNF, TrkB, MBP and PLP expression. Remyelination inhibitor TGFβ gene expression was downregulated in Fgfr1^ind-/-mice (p ≤ 0.05), LINGO-1 was not regulated. There were no differences in the number of oligodendrocytes between Fgfr1^ind-/-mice and controls.

Conclusions These findings suggest that conditional knock out of oligodendroglial FGFR1 protects myelin through downregulation of pERK and decreased expression of the remyelination inhibitor TGFβ. Knock out of oligodendroglial FGFR1 does not affect the number of oligodendrocytes. These data indicate that oligodendroglial FGFR1 causes damage to myelin.

Authors/Disclosures
Vinothkumar Rajendran (Justus-Liebig University) PRESENTER	Mr. Rajendran has nothing to disclose.
	No disclosure on file
Ranjithkumar Rajendran (Justus Liebig University)	Mr. Rajendran has nothing to disclose.
Martin Berghoff, MD, FAAN (BundeswehrZentralkrankenhaus Koblenz)	Dr. Berghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen Idec. Dr. Berghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Berghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Berghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MerckSerono. Dr. Berghoff has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb.

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