The slow Wallerian degeneration gene in vivo protects motor axons but not their cell bodies after avulsion and neonatal axotomy
The slow Wallerian degeneration gene in vivo protects motor axons but not their cell bodies after avulsion and neonatal axotomy
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DOI：
10.1111/j.1460-9568.2006.05103.x
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发表时间：
2006-10-01
影响因子：
3.4
通讯作者：
Coleman, Michael P.
中科院分区：
文献类型：
--
作者：
Adalbert, Robert;Nogradi, Antal;Coleman, Michael P.
缓慢沃勒变性基因（Wld（S））在小鼠和大鼠中延迟沃勒变性和轴突病理数周。有趣的是，在一些体内模型中，神经元细胞死亡也被延迟，在进行性运动神经元病小鼠中最引人注目。在此，我们检验了Wld（S）对体内运动神经元细胞体具有直接保护作用的假设。脊髓内撕脱相应的前根，诱导大鼠L4运动神经元细胞死亡。这同时去除了大部分的运动轴突，最大限度地减少了对轴突的保护作用可以二次拯救细胞体的可能性。对照组和Wld（S）组运动神经元的存活率无显著差异，提示Wld（S）基因对胞体无直接保护作用。我们还测试了Wld（S）大鼠新生神经损伤后运动神经元凋亡死亡的任何延迟，发现与Wld（S）小鼠不同，Wld（S）大鼠在细胞死亡方面没有延迟。然而，相应的远端轴突被保存下来，证实运动神经元细胞体和运动轴突通过不同的机制死亡。因此，Wld（S）不直接阻止运动神经元细胞体的死亡。因此，在轴突或重要轴突残端保留的几种疾病和损伤模型中观察到的神经元细胞体的保护最有可能继发于轴突保护。
The slow Wallerian degeneration gene (Wld(S)) delays Wallerian degeneration and axon pathology for several weeks in mice and rats. Interestingly, neuronal cell death is also delayed in some in vivo models, most strikingly in the progressive motoneuronopathy mouse. Here, we tested the hypothesis that Wld(S) has a direct protective effect on motoneurone cell bodies in vivo. Cell death was induced in rat L4 motoneurones by intravertebral avulsion of the corresponding ventral roots. This simultaneously removed most of the motor axon, minimizing the possibility that the protective effect toward axons could rescue cell bodies secondarily. There was no significant difference between the survival of motoneurones in control and Wld(S) rats, suggesting that the Wld(S) gene has no direct protective effect on cell bodies. We also tested for any delay in apoptotic motoneurone death following neonatal nerve injury in Wld(S) rats and found that, unlike Wld(S) mice, Wld(S) rats show no delay in cell death. However, the corresponding distal axons were preserved, confirming that motoneurone cell bodies and motor axons die by different mechanisms. Thus, Wld(S) does not directly prevent death of motoneurone cell bodies. It follows that the protection of neuronal cell bodies observed in several disease and injury models where axons or significant axonal stumps remain is most probably secondary to axonal protection.