title: Sprouting of axonal collaterals after spinal cord injury is prevented by delayed axonal degeneration.
abstract: After an incomplete spinal cord injury (SCI), partial recovery of locomotion is accomplished with time. Previous studies have established a functional link between extension of axon collaterals from spared spinal tracts and locomotor recovery after SCI, but the tissular signals triggering collateral sprouting have not been identified. Here, we investigated whether axonal degeneration after SCI contributes to the sprouting of collaterals from axons spared after injury. To this end, we evaluated collateral sprouting from BDA-labeled uninjured corticospinal axons after spinal cord hemisection (SCI(H)) in wild type (WT) mouse and Wld(S) mouse strains, which shows a significant delay in Wallerian degeneration after injury. After SCI(H), spared fibers of WT mice extend collateral sprouts to both intact and denervated sides of the spinal cord distant from the injury site. On the contrary, in the Wld(S) mice collateral sprouting from spared fibers was greatly reduced after SCI(H). Consistent with a role for collateral sprouting in functional recovery after SCI, locomotor recovery after SCI(H) was impaired in Wld(S) mice compared to WT animals. In conclusion, our results identify axonal degeneration as one of the triggers for collateral sprouting from the contralesional uninjured fibers after an SCI(H). These results open the path for identifying molecular signals associated with tissular changes after SCI that promotes collateral sprouting and functional recovery.
authors: Millenium Nucleus for Regenerative Biology, Faculty of Biology, Pontificia Universidad Catolica de Chile, Santiago, Chile. Electronic address: etcollyer@uc.cl.
authors: E
authors: E
authors: Collyer
authors: Millenium Nucleus for Regenerative Biology, Faculty of Biology, Pontificia Universidad Catolica de Chile, Santiago, Chile. Electronic address: alecatenaccio@gmail.com.
authors: A
authors: A
authors: Catenaccio
authors: Millenium Nucleus for Regenerative Biology, Faculty of Biology, Pontificia Universidad Catolica de Chile, Santiago, Chile. Electronic address: dlemaitrem@gmail.com.
authors: D
authors: D
authors: Lemaitre
authors: Millenium Nucleus for Regenerative Biology, Faculty of Biology, Pontificia Universidad Catolica de Chile, Santiago, Chile. Electronic address: paula.diaz@cinv.cl.
authors: P
authors: P
authors: Diaz
authors: Millenium Nucleus for Regenerative Biology, Faculty of Biology, Pontificia Universidad Catolica de Chile, Santiago, Chile. Electronic address: vicentevalenzuela@gmail.com.
authors: V
authors: V
authors: Valenzuela
authors: Millenium Nucleus for Regenerative Biology, Faculty of Biology, Pontificia Universidad Catolica de Chile, Santiago, Chile. Electronic address: fbronfman@bio.puc.cl.
authors: F
authors: F
authors: Bronfman
authors: Millenium Nucleus for Regenerative Biology, Faculty of Biology, Pontificia Universidad Catolica de Chile, Santiago, Chile; Neurounion Biomedical Foundation, Santiago, Chile. Electronic address: fcourt@bio.puc.cl.
authors: F A
authors: FA
authors: Court
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology / Q000648:ultrastructure; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D009154:Mutation / Q000235:genetics; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D011597:Psychomotor Performance / Q000502:physiology; D011712:Pyramidal Tracts / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors; D014855:Wallerian Degeneration / Q000209:etiology* / Q000235:genetics
chemical_list: D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C442580:Wld protein, mouse
keywords: Collateral sprouting; Corticospinal neurons; Hemisection; Spinal cord injury; Wallerian degeneration; Wld(S)