title: Decreased anti-regenerative effects after spinal cord injury in spry4-/- mice.
abstract: Previously, we have demonstrated a role for fibroblast growth factor (Fgf) in spinal cord regeneration in both zebrafish and mouse. We have shown that exogenous Fgf2 treatment attenuates astrocytic gliosis and induces glia cells to become progenitors that undergo neurogenesis as well as differentiating into bipolar astrocytes that support axonal regeneration (Goldshmit et al., 2012, 2014). One of the downstream signaling target genes of Fgf is spry4, which acts as a feedback inhibitor for Fgf signaling. In this study we examined the effects of increased endogenous Fgf signaling, in spry4-/- mice, on the early events that occur after spinal cord injury (SCI). We demonstrate that in spry4-/- mice inflammatory responses, such as tumor necrosis factor α (TNFα) secretion and macrophage/neutrophil invasion into the lesion site are reduced. In addition, astrocytic gliosis is attenuated and neuronal survival is increased. These results further support a pro-regenerative role of Fgf after SCI, and suggest that increased endogenous Fgf signaling after SCI may contribute to functional recovery and therefore presents this pathway as a target for new therapy development.
authors.affiliation: Australian Regenerative Medicine Institute, Monash University, VIC, Australia; Department of Neurobiology, Tel Aviv University, Israel. Electronic address: yona.goldshmit@med.monash.edu.au.
authors.forename: Y
authors.initials: Y
authors.lastname: Goldshmit
authors.affiliation: Australian Regenerative Medicine Institute, Monash University, VIC, Australia; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Department of Ophthalmology, The University of Melbourne, East Melbourne, VIC, Australia.
authors.forename: F
authors.initials: F
authors.lastname: Frisca
authors.affiliation: Australian Regenerative Medicine Institute, Monash University, VIC, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Kaslin
authors.affiliation: Australian Regenerative Medicine Institute, Monash University, VIC, Australia.
authors.forename: A R
authors.initials: AR
authors.lastname: Pinto
authors.affiliation: Australian Regenerative Medicine Institute, Monash University, VIC, Australia.
authors.forename: J-K K Y
authors.initials: JK
authors.lastname: Tang
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Department of Ophthalmology, The University of Melbourne, East Melbourne, VIC, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Pébay
authors.affiliation: Department of Neurobiology, Tel Aviv University, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Pinkas-Kramarski
authors.affiliation: Australian Regenerative Medicine Institute, Monash University, VIC, Australia. Electronic address: peter.currie@monash.edu.
authors.forename: P D
authors.initials: PD
authors.lastname: Currie
mesh_terms: D000818:Animals; D002470:Cell Survival; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D005911:Gliosis / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis; D009457:Neuroglia / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D058630:Spinal Cord Regeneration / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; C499037:Spry4 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2
keywords: astrocytes; inflammation; spinal cord injury; spry4−/−