Stone J D, Peterson A P, Eyer J, Oblak T G, Sickles D W
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, Georgia 30912, USA.
J Neurosci. 2001 Apr 1;21(7):2278-87. doi: 10.1523/JNEUROSCI.21-07-02278.2001.
Axonal neurofilament (NF) accumulations occur before development of symptoms and before other pathological changes among idiopathic neurodegenerative diseases and toxic neuropathies, suggesting a cause-effect relationship. The dependence of symptoms and axonal degeneration on neurofilament accumulation has been tested here in a transgenic mouse model (Eyer and Peterson, 1994) lacking axonal NFs and using two prototypic toxicant models. Chronic acrylamide (ACR) or 2,5-hexanedione exposure resulted in progressive and cumulative increases in sensorimotor deficits. Neurobehavioral tests demonstrated similar expression of neurotoxicity in transgenic (T) mice and their nontransgenic (NT) littermates (containing normal numbers of axonal NFs). Axonal lesions were frequently observed after exposure to either toxicant. Quantitation of ACR-induced lesions demonstrated the distal location of pathology and equal susceptibility of T and NT axons. We conclude that axonal NFs have no effect on neurotoxicity and the pattern of pathology in these mammalian toxic neuropathies. These results also suggest that the role of neurofilament accumulation in the pathogenesis of neurodegenerative diseases requires careful evaluation.
在特发性神经退行性疾病和中毒性神经病中，轴突神经丝（NF）聚集在症状出现之前以及其他病理变化之前就已发生，这表明存在因果关系。在此，我们利用一个缺乏轴突NF的转基因小鼠模型（Eyer和Peterson，1994年）并采用两种典型的毒物模型，对症状和轴突变性对神经丝聚集的依赖性进行了测试。长期接触丙烯酰胺（ACR）或2,5 -己二酮会导致感觉运动功能障碍逐渐累积增加。神经行为测试表明，转基因（T）小鼠及其非转基因（NT）同窝小鼠（含有正常数量的轴突NF）的神经毒性表达相似。接触任何一种毒物后都经常观察到轴突损伤。对ACR诱导损伤进行定量分析表明，病理变化位于远端，且T和NT轴突的易感性相同。我们得出结论，轴突NF对这些哺乳动物中毒性神经病的神经毒性和病理模式没有影响。这些结果还表明，神经丝聚集在神经退行性疾病发病机制中的作用需要仔细评估。
