title: Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury.
abstract: Previous studies indicated that the expression of neuropsin, a serine protease, is induced in mature oligodendrocytes after injury to the CNS. The pathophysiology of spinal cord injury (SCI) involves primary and secondary mechanisms, the latter contributing further to permanent losses of function. To explore the role of neuropsin after SCI, histochemical and behavioral analyses were performed in wild-type (WT) and neuropsin-deficient (neuropsin(-/-)) mice using a crush injury model, a well-characterized and consistently reproducible model of SCI. In situ hybridization revealed that neuropsin mRNA expression was induced in the spinal cord white matter from WT mice after crush SCI, peaking at day 4. Neuropsin(-/-) mice showed attenuated demyelination, oligodendrocyte death, and axonal damage after SCI. Although axonal degeneration in the corticospinal tract was obvious caudal to the lesion site in both strains of mice after SCI, the number of surviving nerve fibers caudal to the lesion was significantly larger in neuropsin(-/-) mice than WT mice. Behavioral analysis revealed that the recovery at days 10-42 was significantly improved in neuropsin(-/-) mice compared with WT mice in spite of the severe initial hindlimb impairments due to SCI in both strains. These observations suggest that neuropsin is involved in the secondary phase of the pathogenesis of SCI mediated by demyelination, oligodendrocyte death, and axonal degeneration.
authors.affiliation: Department of Functional Anatomy and Neuroscience, Asahikawa Medical College, 2-1-1-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan. ryujit@md.okayama-u.ac.jp
authors.forename: R
authors.initials: R
authors.lastname: Terayama
authors.forename: Y
authors.initials: Y
authors.lastname: Bando
authors.forename: K
authors.initials: K
authors.lastname: Murakami
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Kishibe
authors.forename: S
authors.initials: S
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D001931:Brain Mapping; D016923:Cell Death / Q000235:genetics; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology; D006429:Hemiplegia / Q000235:genetics / Q000503:physiopathology; D017403:In Situ Hybridization; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000235:genetics; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020127:Recovery of Function / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D014855:Wallerian Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D012333:RNA, Messenger; D007610:Kallikreins; C114664:Prss19 protein, mouse