title: Overexpression of the Fibroblast Growth Factor Receptor 1 (FGFR1) in a Model of Spinal Cord Injury in Rats.
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.
authors.affiliation: Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King's College London, London, SE1 1UL, United Kingdom.
authors.forename: Barbara
authors.initials: B
authors.lastname: Haenzi
authors.affiliation: Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King's College London, London, SE1 1UL, United Kingdom.
authors.forename: Katharina
authors.initials: K
authors.lastname: Gers-Barlag
authors.affiliation: Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King's College London, London, SE1 1UL, United Kingdom.
authors.forename: Halima
authors.initials: H
authors.lastname: Akhoundzadeh
authors.affiliation: Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King's College London, London, SE1 1UL, United Kingdom.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hutson
authors.affiliation: Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King's College London, London, SE1 1UL, United Kingdom.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Menezes
authors.affiliation: 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.
authors.forename: Mary Bartlett
authors.initials: MB
authors.lastname: Bunge
authors.affiliation: Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King's College London, London, SE1 1UL, United Kingdom.
authors.forename: Lawrence D F
authors.initials: LD
authors.lastname: Moon
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D009416:Nerve Regeneration / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011712:Pyramidal Tracts / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000473:pathology / Q000628:therapy
chemical_list: C496350:Fgfr1 protein, rat; D051496:Receptor, Fibroblast Growth Factor, Type 1