title: c-Jun N-terminal kinase induces axonal degeneration and limits motor recovery after spinal cord injury in mice.
abstract: c-Jun N-terminal kinase (JNK) mediates neuronal death in response to stress and injury in the CNS and peripheral nervous system. Here, we show that JNK also regulates retrograde axonal degeneration (axonal dieback) after spinal cord injury (SCI) in mice. Activated phospho-JNK was highly expressed in damaged corticospinal tract (CST) axons after thoracic SCI by hemisection. Local administration of SP600125, a JNK inhibitor, prevented accumulation of amyloid-β precursor protein and retraction of the severed CST axons as well as preserved the axonal arbors rostral to the injury site. The treatment with SP600125 also improved functional recovery of the hindlimbs, assessed by Basso mouse scale open-field scores and the grid-walking test. In Jnk1(-/-) and Jnk3(-/-) mice, we observed prevention of axonal degeneration and enhancement of motor recovery after SCI. These results indicate that both JNK1 and JNK3 induce axonal degeneration and limit motor recovery after SCI. Thus, a JNK inhibitor may be a suitable therapeutic agent for SCI.
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita-shi, Osaka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.forename: Sachiko
authors.initials: S
authors.lastname: Lee
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Akinobu
authors.initials: A
authors.lastname: Sato
authors.forename: Koichi
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kishima
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yoshimine
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048057:Mitogen-Activated Protein Kinase 10 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics*; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000502:physiology*; D009416:Nerve Regeneration / Q000187:drug effects / Q000235:genetics; D010243:Paralysis / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D020127:Recovery of Function / Q000187:drug effects / Q000235:genetics; D013119:Spinal Cord Injuries / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D014855:Wallerian Degeneration / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology
chemical_list: D000873:Anthracenes; C432165:pyrazolanthrone; D048057:Mitogen-Activated Protein Kinase 10; D048055:Mitogen-Activated Protein Kinase 8