title: Inhibition of spinal c-Jun-NH2-terminal kinase (JNK) improves locomotor activity of spinal cord injured rats.
abstract: Mitogen-activated protein kinases (MAPKs) have been implicated in central nervous system injuries, yet the roles within neurodegeneration following spinal cord injury (SCI) still remain partially elucidated. We aimed to investigate the changes in expression of the three MAPKs following SCI and the role of spinal c-jun-NH2-terminal kinase (JNK) in motor impairment following the lesion. SCI induced at the T9 level resulted in enhanced expression of phosphorylated MAPKs shortly after trauma. SCI increased spinal cord myeloperoxidase levels, indicating a local neutrophil infiltration, and elevated the number of spinal apoptotic cells. Intrathecal administration of a specific inhibitor of JNK phosphorylation, SP600125, given at 1 and 4h after SCI, reduced the p-JNK expression, the number of spinal apoptotic cells and many of the histological signs of spinal injury. Notably, restoration of locomotor performance was clearly ameliorated by SP600125 treatment. Altogether, the results demonstrate that SCI induces activation of spinal MAPKs and that JNK plays a major role in mediating the deleterious consequences of spinal injury, not only at the spinal level, but also those regarding locomotor function. Therefore, inhibition of JNK activation in the spinal cord shortly after trauma might constitute a feasible therapeutic strategy for the functional recovery from SCI.
authors.affiliation: Department of Pharmacology, Universidade Federal de Santa Catarina, Florianopolis, SC, Brazil. Electronic address: ac.martini@uci.edu.
authors.forename: Alessandra C
authors.initials: AC
authors.lastname: Martini
authors.affiliation: Department of Pharmacology, Universidade Federal de Santa Catarina, Florianopolis, SC, Brazil.
authors.forename: Stefânia
authors.initials: S
authors.lastname: Forner
authors.affiliation: Department of Pharmacology, Universidade Federal de Santa Catarina, Florianopolis, SC, Brazil.
authors.forename: Janice
authors.initials: J
authors.lastname: Koepp
authors.affiliation: Department of Pharmacology, Universidade Federal de Santa Catarina, Florianopolis, SC, Brazil.
authors.forename: Giles Alexander
authors.initials: GA
authors.lastname: Rae
mesh_terms: D000818:Animals; D017209:Apoptosis; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D009043:Motor Activity; D020556:Neutrophil Infiltration; D010766:Phosphorylation; D017208:Rats, Wistar; D013116:Spinal Cord / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases
keywords: JNK; Locomotor recovery; Mitogen-activated protein kinases; Spinal cord injury