FGF2 and FGFR1 Signaling Regulate Functional Recovery Following Cuprizone Demyelination

Overview

Journal Neurosci Lett

Specialty Neurology

Date 2013 May 21

PMID 23684572

Citations 21

Authors

Amanda J Mierzwa

Yong-Xing Zhou

Norah Hibbits

Adam C Vana

Regina C Armstrong

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

FGF/FGFR system in the central nervous system demyelinating disease: Recent progress and implications for multiple sclerosis.

Zhang Q, Chen Z, Zhang K, Zhu J, Jin T CNS Neurosci Ther. 2023; 29(6):1497-1511.

PMID: 36924298 PMC: 10173727. DOI: 10.1111/cns.14176.

Sex Differences in the Behavioural Aspects of the Cuprizone-Induced Demyelination Model in Mice.

Paton K, Hong S, Biggerstaff A, Kivell B Brain Sci. 2022; 12(12).

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Lysophosphatidic acid signaling via LPA : A negative modulator of developmental oligodendrocyte maturation.

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A Glance at the Molecules That Regulate Oligodendrocyte Myelination.

Wang S, Wang Y, Zou S Curr Issues Mol Biol. 2022; 44(5):2194-2216.

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Phenytoin promotes the proliferation of oligodendrocytes and enhances the expression of myelin basic protein in the corpus callosum of mice demyelinated by cuprizone.

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PMID: 35362723 DOI: 10.1007/s00221-022-06356-0.

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