IMPAIRED AXONAL REGENERATION IN ACRYLAMIDE INTOXICATION
IMPAIRED AXONAL REGENERATION IN ACRYLAMIDE INTOXICATION
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DOI：
10.1002/neu.480080407
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发表时间：
1977-01-01
期刊：
影响因子：
--
通讯作者：
DRACHMAN, DB
中科院分区：
文献类型：
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作者：
GRIFFIN, JW;PRICE, DL;DRACHMAN, DB
丙烯酰胺是一种神经毒素，已知会损害神经挤压后轴突的再生，并产生结构异常的再生芽。为了探讨这些异常的机制，蛋白质合成和快速轴突运输进行了研究，在丙烯酰胺中毒和对照组大鼠坐骨神经挤压后2周。使用坐骨神经背根神经节的体外制备，两组之间的神经节3 H-亮氨酸掺入没有差异。在这些制备的感觉轴突，并在运动轴突在体内研究，一个较小比例的快速运输的放射性进行超越的挤压在丙烯酰胺再生神经相比，控制再生神经。相关的超微结构研究表明，这种差异反映了受损的丙烯酰胺再生神经的生长，而不是在快速运输异常。丙烯酰胺处理过的芽通常会发育出充满神经丝螺旋的芽囊;许多芽的末端是巨大的生长锥，其中含有膜性细胞器。EM放射自显影显示标记的，快速运输的细胞器中积累的神经丝轮，因此建议，这些细胞器可能被困或阻碍通过这些地区。没有证据表明，生长锥收到的运输蛋白质的量不足，膨胀的结束密集标记，显然气球运输细胞器。丙烯酰胺中毒可能不会通过减少快速运输物质到生长尖端的传递而损害再生。生长锥的显着膨胀被解释为形态学的结果，继续交付的快速运输的细胞器到芽无法利用它们的生长。
Acrylamide is a neurotoxin known to impair regeneration of axons following nerve crush and to produce structurally abnormal regenerating sprouts. To investigate the mechanism of these abnormalities, protein synthesis and fast axonal transport were studied in acrylamide-intoxicated and control rats 2 wk after sciatic nerve crush. Using an in vitro preparation of sciatic nerve-dorsal root ganglion, there was no difference in ganglion 3H-leucine incorporation between the 2 groups. In these preparations of sensory axons, and in motor axons studied in vivo, a smaller proportion of rapidly transported radioactivity was carried beyond the crush in the acrylamide-regenerating nerves compared to the control-regenerating nerves. Correlative ultrastructural studies demonstrated that this difference reflected the impaired outgrowth of the acrylamide-regenerating nerves, rather than an abnormality in fast transport. The acrylamide-treated sprouts often developed swellings filled with whorls of neurofilaments; many sprouts ended in massively enlarged growth cones containing membranous organelles. EM autoradiography showed labeled, rapidly transported organelles accumulated in the neurofilamentous whorls, and therefore suggested that these organelles might be trapped or impeded in passage through these regions. There was no evidence that the growth cones received insufficient amounts of transported protein; the distended endings were densely labeled and apparently ballooned by transported organelles. Acrylamide intoxication probably does not impair regeneration by diminishing the delivery of rapidly transported materials to the growing tip. The marked distention of the growth cones is interpreted as the morphological consequence of continued delivery of rapidly transported organelles into sprouts unable to utilize them in outgrowth.