Ablation of adhesion molecule L1 in mice favours Schwann cell proliferation and functional recovery after peripheral nerve injury
Ablation of adhesion molecule L1 in mice favours Schwann cell proliferation and functional recovery after peripheral nerve injury
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DOI：
10.1093/brain/awp160
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发表时间：
2009-08-01
期刊：
影响因子：
14.5
通讯作者：
Schachner, Melitta
中科院分区：
文献类型：
--
作者：
Guseva, Daria;Angelov, Doychin N.;Schachner, Melitta
粘附分子L1是已知通过促进轴突生长和神经元存活而有益于脊椎动物的成年中枢神经系统中的修复过程的少数粘附分子之一。在周围神经系统中，L1在神经损伤后被髓鞘形成的雪旺氏细胞和再生轴突上调，但其功能作用仍然未知。在这里，我们测试的假设，L1是，在中枢神经系统中，有利于周围神经系统的神经再生进行综合功能和组织学分析的成年L1缺陷小鼠（L1 y/）和野生型（L1 y/）同窝仔。与我们的假设相反，基于视频的定量运动分析显示，在股神经横断和手术修复后412周，L1 y/小鼠的运动恢复比L1 y/小鼠好。运动神经元再生L1 y/小鼠也增强，如由运动神经元的创伤后损失减弱、运动神经再支配的精确性增强、再生运动神经元的细胞体更大和运动神经元的抑制性突触输入的损失减少所指示的。在寻找所观察到的影响的机制，我们分析了周围神经在短时间内（314天）横断后，发现雪旺细胞增殖强烈增强L1 y/与L1 y/小鼠。L1缺陷的雪旺细胞表现出增加的增殖比野生型雪旺细胞，在体内和体外。这些发现表明L1在神经再生中的新作用。我们建议，L1负调节神经损伤后的雪旺细胞增殖，这反过来又限制了再生运动神经元的营养支持功能恢复。
The adhesion molecule L1 is one of the few adhesion molecules known to be beneficial for repair processes in the adult central nervous system of vertebrates by promoting axonal growth and neuronal survival. In the peripheral nervous system, L1 is up-regulated by myelination-competent Schwann cells and regenerating axons after nerve damage but its functional role has remained unknown. Here we tested the hypothesis that L1 is, as in the central nervous system, beneficial for nerve regeneration in the peripheral nervous system by performing combined functional and histological analyses of adult L1-deficient mice (L1y/) and wild-type (L1y/) littermates. Contrary to our hypothesis, quantitative video-based motion analysis revealed better locomotor recovery in L1y/ than in L1y/ mice at 412 weeks after transection and surgical repair of the femoral nerve. Motoneuron regeneration in L1y/ mice was also enhanced as indicated by attenuated post-traumatic loss of motoneurons, enhanced precision of motor reinnervation, larger cell bodies of regenerated motoneurons and diminished loss of inhibitory synaptic input to motoneurons. In search of mechanisms underlying the observed effects, we analysed peripheral nerves at short time-periods (314 days) after transection and found that Schwann cell proliferation is strongly augmented in L1y/ versus L1y/ mice. L1-deficient Schwann cells showed increased proliferation than wild-type Schwann cells, both in vivo and in vitro. These findings suggest a novel role for L1 in nerve regeneration. We propose that L1 negatively regulates Schwann cell proliferation after nerve damage, which in turn restricts functional recovery by limiting the trophic support for regenerating motoneurons.