Overexpression of the Fibroblast Growth Factor Receptor 1 (FGFR1) in a Model of Spinal Cord Injury in Rats

Barbara Haenzi; Katharina Gers-Barlag; Halima Akhoundzadeh; Thomas H Hutson; Sean C Menezes; Mary Bartlett Bunge; Lawrence D F Moon

doi:10.1371/journal.pone.0150541

Overexpression of the Fibroblast Growth Factor Receptor 1 (FGFR1) in a Model of Spinal Cord Injury in Rats

PLoS One. 2016 Mar 25;11(3):e0150541. doi: 10.1371/journal.pone.0150541. eCollection 2016.

Authors

Barbara Haenzi¹, Katharina Gers-Barlag¹, Halima Akhoundzadeh¹, Thomas H Hutson¹, Sean C Menezes¹, Mary Bartlett Bunge², Lawrence D F Moon¹

Affiliations

¹ Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King's College London, London, SE1 1UL, United Kingdom.
² Miami Project to Cure Paralysis, Departments of Cell Biology, Neurological Surgery and Neurology, University of Miami Miller School of Medicine, Miami, FL, 33136, United States of America.

Abstract

Spinal cord injury (SCI) is a severe condition that affects many people and results in high health care costs. Therefore, it is essential to find new targets for treatment. The fibroblast growth factor receptor 1 (FGFR1) signalling pathway has a history of being explored for SCI treatment. Several groups have examined the effect of high availability of different FGFR1 ligands at the injury site and reported corticospinal tract (CST) regeneration as well as improved motor functions. In this study, we investigated overexpression of the FGFR1 in rat corticospinal neurons in vivo after injury (unilateral pyramidotomy) and in cerebellar granule neurons (CGNs) in vitro. We show that overexpression of FGFR1 using AAV1 intracortical injections did not increase sprouting of the treated corticospinal tract and did not improve dexterity or walking in a rat model of SCI. Furthermore, we show that overexpression of FGFR1 in vitro resulted in decreased neurite outgrowth compared to control. Thus, our results suggest that the FGFR1 is not a suitable therapeutic target after SCI.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Axons / metabolism
Axons / pathology
Disease Models, Animal
Humans
Male
Nerve Regeneration / genetics*
Neurons / metabolism
Neurons / pathology
Pyramidal Tracts / growth & development*
Pyramidal Tracts / metabolism
Pyramidal Tracts / pathology
Rats
Receptor, Fibroblast Growth Factor, Type 1 / biosynthesis*
Receptor, Fibroblast Growth Factor, Type 1 / genetics
Signal Transduction
Spinal Cord Injuries / genetics*
Spinal Cord Injuries / pathology
Spinal Cord Injuries / therapy

Substances

Fgfr1 protein, rat
Receptor, Fibroblast Growth Factor, Type 1

Grants and funding

This submission was supported by funding from the Swiss National Science Foundation (SNSF), the Henry Smith Charity, the Wings for Life Spinal Cord Research Foundation, the Miami Project to Cure Paralysis, the National Institute of Neurological Disorders and Stroke (09923) and the Christopher and Dana Reeve Foundation International Research Consortium. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.