Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury
Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury
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DOI：
10.1016/j.neuroscience.2007.05.037
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发表时间：
2007-08-10
期刊：
影响因子：
3.3
通讯作者：
Yoshida, S.
中科院分区：
文献类型：
--
作者：
Terayama, R.;Bando, Y.;Yoshida, S.
以往的研究表明，神经蛋白酶，丝氨酸蛋白酶的表达，诱导在成熟的少突胶质细胞损伤后的中枢神经系统。脊髓损伤（SCI）的病理生理学涉及原发性和继发性机制，后者进一步导致永久性功能丧失。为了探索神经蛋白酶在SCI后的作用，使用挤压损伤模型（一种表征良好且可持续重现的SCI模型）在野生型（WT）和神经蛋白酶缺陷（神经蛋白酶（-/-））小鼠中进行组织化学和行为分析。原位杂交显示，神经蛋白酶mRNA的表达诱导脊髓白色物质从野生型小鼠挤压SCI后，在第4天达到高峰。Neuropsin（-/-）小鼠表现出脊髓损伤后减轻的脱髓鞘，少突胶质细胞死亡和轴突损伤。虽然在皮质脊髓束轴突变性是明显的尾侧的损伤部位在两个品系的小鼠脊髓损伤后，尾侧的损伤的存活神经纤维的数量显着更大的neuropsin（-/-）小鼠比WT小鼠。行为分析显示，与WT小鼠相比，neuropsin（-/-）小鼠在第10-42天的恢复显著改善，尽管在两种品系中由于SCI导致严重的初始后肢损伤。这些观察结果表明，neuropsin参与介导的脱髓鞘，少突胶质细胞死亡和轴突变性的脊髓损伤的发病机制的第二阶段。(c)2007年IBRO。由爱思唯尔有限公司出版。保留所有权利。
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. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.