Day W Antony, Koishi Kyoko, McLennan Ian S
Arizona Research Laboratories, Department of Neuroscience, University of Arizona, Tucson, AZ, USA.
Exp Neurol. 2003 Dec;184(2):857-64. doi: 10.1016/S0014-4886(03)00308-X.
The molecular mechanisms underlying peripheral neuropathies have only been partially elucidated. In particular, the regulatory factors that control the stability and turnover of mature myelin are largely unknown. Transforming growth factor beta 1 (TGF-beta1), and its associated receptors, are expressed by mature Schwann cells. On this basis, we postulated that TGF-beta1 may be an autocrine regulator of mature myelin. This hypothesis was tested by examining the ultrastructure of myelin in adult mice that have a null mutation of their TGF-beta1 gene. We report here that the myelin of these mice is grossly abnormal. At the nodes of Ranvier, the cytoplasmic collars of the Schwann cells were expanded and the myelin had a honeycomb appearance. Focal (tomacula-like) hypermyelin structures were observed in the internodal regions of a significant number of axons in mutant nerve, and were not observed in littermate controls. Axon diameters were within the normal range and no axonal pathology was evident in mutant nerve and macrophages were absent. Results imply that lack of TGF-beta1 may have a direct effect on Schwann cells. We suggest that TGF-beta1 may stabilise compact myelin via an autocrine mechanism.
周围神经病变的分子机制仅得到部分阐明。特别是，控制成熟髓鞘稳定性和更新的调节因子在很大程度上尚不清楚。转化生长因子β1（TGF-β1）及其相关受体由成熟的施万细胞表达。在此基础上，我们推测TGF-β1可能是成熟髓鞘的自分泌调节因子。通过检查TGF-β1基因发生无效突变的成年小鼠的髓鞘超微结构来验证这一假设。我们在此报告，这些小鼠的髓鞘明显异常。在郎飞结处，施万细胞的细胞质环扩张，髓鞘呈蜂窝状外观。在突变神经中，大量轴突的节间区域观察到局灶性（类腊肠样）髓鞘增厚结构，而在同窝对照中未观察到。轴突直径在正常范围内，突变神经中未发现明显的轴突病变，也没有巨噬细胞。结果表明，缺乏TGF-β1可能对施万细胞有直接影响。我们认为，TGF-β1可能通过自分泌机制稳定紧密髓鞘。
