TY - JOUR
T1 - Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury
AU - Terayama, R.
AU - Bando, Y.
AU - Murakami, K.
AU - Kato, K.
AU - Kishibe, M.
AU - Yoshida, S.
N1 - Funding Information:
This work was partly supported by grants from the Ministry of Education, Science, Culture and Sports of Japan, the Noastec Grant, the Akiyama Foundation and the Inamori Foundation. We thank Dr. Sadao Shiosaka for providing neuropsin −/− mice and his comments on this manuscript.
PY - 2007/8/10
Y1 - 2007/8/10
N2 - 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.
AB - 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.
KW - behavior
KW - immunofluorescence labeling
KW - in situ hybridization
KW - secondary injury
KW - serine protease
KW - tract tracing
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U2 - 10.1016/j.neuroscience.2007.05.037
DO - 10.1016/j.neuroscience.2007.05.037
M3 - Article
C2 - 17629414
AN - SCOPUS:34547683904
SN - 0306-4522
VL - 148
SP - 175
EP - 187
JO - Neuroscience
JF - Neuroscience
IS - 1
ER -