CHANGES IN NEUROFILAMENT TRANSPORT COINCIDE TEMPORALLY WITH ALTERATIONS IN THE CALIBER OF AXONS IN REGENERATING MOTOR FIBERS
CHANGES IN NEUROFILAMENT TRANSPORT COINCIDE TEMPORALLY WITH ALTERATIONS IN THE CALIBER OF AXONS IN REGENERATING MOTOR FIBERS
复制标题
DOI：
10.1083/jcb.101.4.1332
复制
发表时间：
1985-01-01
影响因子：
7.8
通讯作者：
PRICE, DL
中科院分区：
文献类型：
--
作者：
HOFFMAN, PN;THOMPSON, GW;PRICE, DL
通过轴突运输递送神经丝已被认为是调节轴突口径的重要机制。如果这一假设是正确的，轴突口径的改变应该与神经丝向轴突输送的变化一致。本研究的目的是确定是否在横断运动纤维的近端残端的轴突的口径的改变之前，符合，或发生大幅晚于通过轴突运输的神经丝的交付的变化。7周龄大鼠坐骨神经损伤后3d ~ 12 wk，脊髓内注射[35 S]蛋氨酸标记腰运动神经元。在标记的神经元之间的3天和6周后轴突切断，神经丝蛋白的相对量在缓慢的组成部分，反映了145-kD的神经丝蛋白微管蛋白的放射性的比率，减少到30-40%的控制值。此外，通过免疫印迹法测定，这些神经纤维中的神经丝蛋白和微管蛋白的量分别减少了四倍。因此，标记的神经丝蛋白与微管蛋白的比例的变化与神经纤维中这些蛋白质的数量的可比变化相关。传递到轴突的神经丝蛋白数量的减少与轴突口径的减少在时间上一致。再生发生后，神经丝蛋白的递送恢复到轴突切开前的水平（即，轴突切断后8周），并且随着这些轴突的正常年龄相关的径向生长的恢复，口径恢复。因此，轴突口径的变化在时间上与神经丝蛋白的传递变化一致。这些结果表明，大多数的神经丝在这些运动纤维不断向前的方向移动的一部分，轴突运输的缓慢组成部分，神经丝的运输起着重要的作用，在调节这些轴突的口径。
The delivery of neurofilaments via axonal transport has been proposed as an important mechanism for regulating axonal caliber. If this hypothesis is correct, alterations in axonal caliber should appear coincident with changes in the delivery of neurofilaments to the axon. The purpose of this study was to determine whether alterations in the caliber of axons in the proximal stumps of transected motor fibers precede, coincide with, or occur substantially later than changes in the delivery of neurofilaments via axonal transport. Between 3 d and 12 wk after crushing the sciatic nerves of 7-wk-old-rats, lumbar motor neurons were labeled by the intraspinal injection of [35S]methionine. In the neurons labeled between 3 d and 6 wk after axotomy, the relative amount of neurofilament protein in the slow component, as reflected by the ratio of the radioactivities of the 145-kD neurofilament protein to tubulin, was reduced to 30-40% of the control value. Moreover, as determined by immunoreactivity on blots, the amounts of neurofilament protein and tubulin in these nerve fibers were reduced fourfold, respectively. Thus, changes in the ratio of labeled neurofilament protein to tubulin correlated with comparable changes in the quantities of these proteins in nerve fibers. This decrease in the quantity of neurofilament proteins delivered to axons coincided temporally with reductions in axonal caliber. After regeneration occurred, the delivery of neurofilament proteins returned to pre-axotomy levels (i.e., 8 wk after axotomy), and caliber was restored with resumption of normal age-related radial growth of these axons. Thus, changes in axonal caliber coincided temporally with alterations in the delivery of neurofilament proteins. These results suggest that the majority of neurofilaments in these motor fibers continuously move in the anterograde direction as part of the slow component of axonal transport and that the transport of neurofilaments plays an important role in regulating the caliber of these axons.