Adhesion molecule L1 overexpressed under the control of the neuronal Thy-1 promoter improves myelination after peripheral nerve injury in adult mice
Adhesion molecule L1 overexpressed under the control of the neuronal Thy-1 promoter improves myelination after peripheral nerve injury in adult mice
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DOI：
10.1016/j.expneurol.2011.02.018
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发表时间：
2011-06-01
影响因子：
5.3
通讯作者：
Schachner, Melitta
中科院分区：
文献类型：
--
作者：
Guseva, Daria;Zerwas, Meike;Schachner, Melitta
L1是一种有利于中枢神经系统（CNS）损伤后功能和解剖恢复的粘附分子。其在周围神经系统（PNS）再生中的作用尚不清楚。基因敲除小鼠的研究令人惊讶地发现，L1通过抑制雪旺细胞增殖对功能性神经再生有负面影响。为了进一步阐明L1在PNS再生中的作用，我们使用了一种新的转基因小鼠，在神经元特异性的Thy-1启动子的控制下，在神经元中过表达L1，但在PNS或CNS胶质细胞中不表达L1。在不损伤神经的情况下，与野生型小鼠相比，转基因表达对股神经功能、股四头肌运动神经元数量和股神经有髓轴突数量没有影响，但导致感觉隐神经髓鞘形成轻微减少，股四头肌运动神经分支有髓轴突神经丝密度增加。股骨神经损伤后，L1过表达对功能恢复的时间和程度无影响。再生四头肌运动神经元的数量、肌肉再神经支配的精确度、再生神经的轴突数量和节间长度也未受影响。尽管缺乏功能影响，但转基因小鼠的运动和感觉股神经分支的髓鞘形成明显改善，运动神经元周围抑制终端的丧失减弱。我们的研究结果表明，L1是受损PNS中髓鞘形成的调节因子，值得研究旨在利用外源性L1改善脱髓鞘PNS和CNS疾病的功能。(C) 2011爱思唯尔公司版权所有。
L1 is an adhesion molecule favorably influencing the functional and anatomical recoveries after central nervous system (CNS) injuries. Its roles in peripheral nervous system (PNS) regeneration are less well understood. Studies using knockout mice have surprisingly revealed that L1 has a negative impact on functional nerve regeneration by inhibiting Schwann cell proliferation. To further elucidate the roles of L1 in PNS regeneration, here we used a novel transgenic mouse overexpressing L1 in neurons, but not in PNS or CNS glial cells, under the control of a neuron-specific Thy-1 promoter. Without nerve injury, the transgene expression, as compared to wild-type mice, had no effect on femoral nerve function, numbers of quadriceps motoneurons and myelinated axons in the femoral nerve but resulted in slightly reduced myelination in the sensory saphenous nerve and increased neurofilament density in myelinated axons of the quadriceps motor nerve branch. After femoral nerve injury, L1 overexpression had no impact on the time course and degree of functional recovery. Unaffected were also numbers of regenerated quadriceps motoneurons, precision of muscle reinnervation, axon numbers and internodal lengths in the regenerated nerves. Despite the lack of functional effects, myelination in the motor and sensory femoral nerve branches was significantly improved and loss of perisomatic inhibitory terminals on motoneurons was attenuated in the transgenic mice. Our results indicate that L1 is a regulator of myelination in the injured PNS and warrant studies aiming to improve function in demyelinating PNS and CNS disorders using exogenous L1. (C) 2011 Elsevier Inc. All rights reserved.