Terada M, Yasuda H, Kikkawa R
Third Department of Medicine, Shiga University of Medical Science, Otsu, Japan.
J Neurol Sci. 1998 Feb 18;155(1):23-30. doi: 10.1016/s0022-510x(97)00269-4.
It is known that Wallerian degeneration (WD) is prerequisite for nerve regeneration, which is impaired in experimental diabetic rats. To elucidate the effect of hyperglycemia on WD, we studied the time course of WD after axotomy in streptozocin-diabetic (DM) and control rats. Sciatic nerves were removed at several time points after axotomy (days 0-24). Morphometric analysis indicated that WD was delayed in DM throughout experimental period. Quantitative immunohistochemical analysis showed that the early recruitment of macrophage did not differ between the two groups, although its late recruitment was significantly decreased in DM at 15 and 24 days post-axotomy, which suggested that the macrophage-associated process did not contribute to delayed WD in diabetes. Immunoblot analysis showed a delay in the degradation of neurofilaments (NFs) in DM during WD. Phosphorylated NFs detected by SMI31 were more recognized in DM, while the opposite was true for unphosphorylated NFs detected by SMI32. Since it is known that the sensitivity of NF to calpain-mediated proteolysis is modulated by its carboxyl-terminal phosphorylation state and phosphorylated NFs are resistant to calpains, we concluded that abnormal NF phosphorylation state in diabetes could be one of the mechanisms by which axonal degeneration was delayed.
已知沃勒变性（WD）是神经再生的前提条件，而在实验性糖尿病大鼠中该过程受损。为阐明高血糖对沃勒变性的影响，我们研究了链脲佐菌素诱导的糖尿病（DM）大鼠和对照大鼠轴突切断后沃勒变性的时间进程。在轴突切断后的几个时间点（0 - 24天）取出坐骨神经。形态学分析表明，在整个实验期间，糖尿病大鼠的沃勒变性均延迟。定量免疫组化分析显示，两组巨噬细胞的早期募集无差异，尽管在轴突切断后15天和24天，糖尿病大鼠巨噬细胞的晚期募集显著减少，这表明巨噬细胞相关过程并非导致糖尿病中沃勒变性延迟的原因。免疫印迹分析显示，糖尿病大鼠在沃勒变性期间神经丝（NFs）的降解延迟。用SMI31检测到的磷酸化神经丝在糖尿病大鼠中更易被识别，而用SMI32检测到的非磷酸化神经丝则相反。由于已知神经丝对钙蛋白酶介导的蛋白水解的敏感性受其羧基末端磷酸化状态调节，且磷酸化神经丝对钙蛋白酶有抗性，我们得出结论，糖尿病中神经丝异常的磷酸化状态可能是轴突变性延迟的机制之一。
