Berciano M T, Calle E, Fernández R, Lafarga M
Department of Anatomy and Cell Biology, Faculty of Medicine, Santander, Spain.
Acta Neuropathol. 1998 Mar;95(3):269-79. doi: 10.1007/s004010050797.
We have used an experimental model of tellurium(Te)-induced demyelinating neuropathy in the rat to study cellular mechanisms involved in regulating Schwann cell (SC) numbers during remyelination. Starting at postnatal day 21, weaned rats were fed a diet containing 1.1% elemental Te. Following 7 days of Te treatment and at several time points of post-tellurium treatment (PTe), the animals were processed for ultrastructural analysis, SC nuclei quantification and teased fibre preparations. It is well-established that Te induces a transient demyelinating/remyelinating sequence in sciatic nerves. The loss of the myelin sheath in this neuropathy produces active proliferation and overproduction of immature SCs. By electron microscopy analysis most mitotic SCs were located along demyelinated segments. Quantitative determination of SC nuclei per transverse section of sciatic nerve revealed a dramatic increase of SCs at 2 days PTe relative to control nerves. The number of SC nuclei then decreased progressively during the long-term period of recovery studied (330 days PTe). In Te-treated rats, SCs undergoing cell death were regularly found within the nerve fibre compartment, especially on demyelinated segments. Dying cells exhibited morphological features of apoptosis and appeared enclosed by lamellar processes of adjacent healthy SCs in extracellular compartments. Both healthy immature SCs and endoneurial macrophages were involved in the phagocytosis of apoptotic SCs. Particularly during remyelination, supernumerary endoneurial SCs were observed surrounding myelinated fibres. These cells progressively became atrophic with a morphological phenotype similar so that of "onion bulb" cells. On the other hand, teased fibre measurements revealed a remarkable permanent internodal shortening in remyelinated fibres from Te-treated sciatic nerves. These results indicate that a portion of redundant immature SCs are susceptible to elimination by apoptosis. However, other distinct biological mechanisms such as the persistence of supernumerary SCs in the endoneurium and the shortening of internodal lengths are also involved in regulating SC numbers during the remyelination stage.
我们利用碲（Te）诱导大鼠脱髓鞘性神经病的实验模型，来研究在髓鞘再生过程中调节雪旺细胞（SC）数量的细胞机制。从出生后第21天开始，给断奶大鼠喂食含1.1%元素碲的饮食。在碲处理7天后以及碲处理后（PTe）的几个时间点，对动物进行超微结构分析、SC细胞核定量和 teased纤维制备。众所周知，碲会在坐骨神经中诱导短暂的脱髓鞘/髓鞘再生序列。这种神经病中髓鞘的丧失会导致未成熟SCs的活跃增殖和过度产生。通过电子显微镜分析，大多数有丝分裂的SCs位于脱髓鞘节段。对坐骨神经每个横切面的SC细胞核进行定量测定，结果显示相对于对照神经，在PTe第2天时SCs显著增加。然后，在所研究的长期恢复期间（PTe 330天），SC细胞核的数量逐渐减少。在经碲处理的大鼠中，在神经纤维区域内经常发现正在经历细胞死亡的SCs，尤其是在脱髓鞘节段。垂死细胞表现出凋亡的形态特征，并且在细胞外区域似乎被相邻健康SCs的板层状突起所包围。健康的未成熟SCs和神经内膜巨噬细胞都参与了凋亡SCs的吞噬作用。特别是在髓鞘再生期间，观察到超数的神经内膜SCs围绕着有髓纤维。这些细胞逐渐萎缩，其形态表型类似于“洋葱球”细胞。另一方面，teased纤维测量显示，来自经碲处理的坐骨神经的髓鞘再生纤维中存在明显的永久性节间缩短。这些结果表明，一部分多余的未成熟SCs易于通过凋亡被清除。然而，其他不同的生物学机制，如神经内膜中超数SCs的持续存在和节间长度的缩短，也参与了髓鞘再生阶段SC数量的调节。
