Disruption of the midkine gene (Mdk) delays degeneration and regeneration in injured peripheral nerve
Disruption of the midkine gene (Mdk) delays degeneration and regeneration in injured peripheral nerve
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DOI：
10.1002/jnr.22127
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发表时间：
2009-10
影响因子：
4.2
通讯作者：
H. Sakakima;Y. Yoshida;Yoshiki Yamazaki;F. Matsuda;Masako Ikutomo;K. Ijiri;H. Muramatsu;Takashi Muramatsu;Kenji Kadomatsu
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文献类型：
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作者：
H. Sakakima;Y. Yoshida;Yoshiki Yamazaki;F. Matsuda;Masako Ikutomo;K. Ijiri;H. Muramatsu;Takashi Muramatsu;Kenji Kadomatsu
中期因子（MK）是一种生长因子，参与各种组织，特别是神经组织的发育和修复。MK在受损的周围神经中充当修复性神经营养因子。通过比较冷冻损伤后野生型（Mdk+/+）小鼠与MK缺陷型（Mdk −/−）小鼠，探索MK在坐骨神经变性和再生中的假定作用。在Mdk−/−小鼠中，观察到再生延迟，之前是减速的沃勒变性（WD）。比目鱼肌的相对湿重缓慢下降，与Mdk+/+小鼠相比，恢复延迟。在再生神经中，无髓鞘轴突分布不均匀，一些轴突含有髓鞘样同心板层体。在比目鱼肌终板中，含有突触小泡的神经末梢在两种小鼠中均消失。在Mdk−/−小鼠中，损伤后终末按钮的突触囊泡中神经末梢的出现延迟。与Mdk +/+小鼠相比，Mdk−/−小鼠的诱发肌电图恢复延迟。我们的研究结果表明，与Mdk +/+小鼠相比，Mdk −/−小鼠的轴突变性和再生延迟，并且延迟的再生与运动功能的延迟恢复有关。这些发现表明，周围神经损伤后MK的缺乏是变性和再生的关键因素，并且MK供应的操纵可能为周围神经损伤的治疗提供有趣的治疗选择。© 2009 Wiley利斯公司
Midkine (MK) is a growth factor implicated in the development and repair of various tissues, especially neural tissues. MK acts as a reparative neurotrophic factor in damaged peripheral nerves. A postulated role of MK in the degeneration and regeneration of sciatic nerves was explored by comparing wild‐type (Mdk+/+) mice with MK‐deficient (Mdk−/−) mice after freezing injury. In the Mdk−/− mice, a regenerative delay was observed, preceded by a decelerated Wallerian degeneration (WD). The relative wet weight of the soleus muscle slowly declined, and recovery was delayed compared with that in the Mdk+/+ mice. In the regenerating nerve, unmyelinated axons were unevenly distributed, and some axons contained myelin‐like, concentrically lamellated bodies. In the endplates of soleus muscles, nerve terminals containing synaptic vesicles disappeared in both mice. In Mdk−/− mice, the appearance of nerve terminals was delayed in synaptic vesicles of terminal buttons after injury. The recovery of evoked electromyogram was delayed in Mdk−/− mice compared with Mdk+/+ mice. Our results suggested a delay in axonal degeneration and regeneration in Mdk−/− mice compared with Mdk+/+ mice, and the delayed regeneration was associated with a delayed recovery of motor function. These findings show that a lack of MK following peripheral nerve injury is a critical factor in degeneration and regeneration, and manipulation of the supply of MK may offer interesting therapeutic options for the treatment of peripheral nerve damage. © 2009 Wiley‐Liss, Inc.