Journal
NEUROSCIENCE LETTERS
Volume 548, Issue -, Pages 280-285Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2013.05.010
Keywords
Remyelination; Corpus callosum; Wheel activity; Sociability; Growth factor; Multiple sclerosis
Categories
Funding
- National Multiple Sclerosis Society [RG3515, RG4224]
- National Institutes for Health [NS39293]
- Center for Neuroscience and Regenerative Medicine (DoD)
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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 weeks) or chronic (12 weeks) demyelination. Plp/CreERT:Fgfr1(fl/fl) mice administered tamoxifen at 10 weeks 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. (C) 2013 The Authors. Published by Elsevier Ireland Ltd. All rights reserved.
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