Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, USA.
J Neurochem. 2011 May;117(3):554-64. doi: 10.1111/j.1471-4159.2011.07226.x. Epub 2011 Mar 21.
Myelin damage can lead to the loss of axonal conduction and paralysis in multiple sclerosis and spinal cord injury. Here, we show that acrolein, a lipid peroxidation product, can cause significant myelin damage in isolated guinea pig spinal cord segments. Acrolein-mediated myelin damage is particularly conspicuous in the paranodal region in both a calcium dependent (nodal lengthening) and a calcium-independent manner (paranodal myelin splitting). In addition, paranodal protein complexes can dissociate with acrolein incubation. Degraded myelin basic protein is also detected at the paranodal region. Acrolein-induced exposure and redistribution of paranodal potassium channels and the resulting axonal conduction failure can be partially reversed by 4-AP, a potassium channel blocker. From this data, it is clear that acrolein is capable of inflicting myelin damage as well as axonal degeneration, and may represent an important factor in the pathogenesis in multiple sclerosis and spinal cord injury.
髓鞘损伤可导致多发性硬化症和脊髓损伤中的轴突传导丧失和瘫痪。在这里，我们表明，丙烯醛，一种脂质过氧化产物，可导致分离的豚鼠脊髓段发生明显的髓鞘损伤。丙烯醛介导的髓鞘损伤在钙依赖性（结区长）和钙非依赖性方式（结旁髓鞘分裂）中均特别明显。此外，结旁蛋白复合物可随丙烯醛孵育而解离。在结旁区还检测到降解的髓鞘碱性蛋白。用钾通道阻滞剂 4-AP 可部分逆转丙烯醛诱导的钾通道暴露和重新分布以及由此导致的轴突传导失败。从这些数据可以清楚地看出，丙烯醛能够造成髓鞘损伤和轴突变性，并且可能是多发性硬化症和脊髓损伤发病机制中的重要因素。
