Regulation of aberrant neurofilament phosphorylation in neuronal perikarya. II. Correlation with continued axonal elongation following axotomy.
Regulation of aberrant neurofilament phosphorylation in neuronal perikarya. II. Correlation with continued axonal elongation following axotomy.
复制标题
神经元周核异常神经丝磷酸化的调节。
DOI：
10.1097/00005072-199109000-00008
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发表时间：
1991
影响因子：
3.2
通讯作者：
Griffin,JW
中科院分区：
文献类型：
--
作者：
Gold,BG;Austin,DR;Griffin,JW
神经丝（NF）通常在神经元胞体中磷酸化程度低，而在轴突中磷酸化程度高。神经元核周体中异常的NF磷酸化已在许多人类和实验性疾病中得到证实。在这项研究中，我们问这些磷酸化的NF（pNF）表位的表达是否依赖于神经横断（轴突切断术）后持续的轴突再生。使用神经毒性化学品丙烯酰胺（AC）测试了这一假设，已知该化学品在全身给药后会抑制轴突再生。首先，我们研究了AC是否在神经元核周体水平上起作用以抑制轴突伸长。全身性、高剂量腹腔内（IP）AC给药（总计150 mg/kg（75 mg/kg × 2））未损害轴突切断诱导的神经元核周体中缓慢轴突运输的重新排序。接下来，我们研究了AC直接阻止轴突生长尖端的神经生长的能力。AC（0.1 M）的神经束膜下注射，在初步研究中发现不产生神经纤维损伤，显着减少神经生长的程度时，近端注射神经挤压，这是由减少的放射性标记的程度和轴突芽在远端残端7天后神经挤压。使用该方案，与对侧盐水注射的压碎神经相比，在AC注射的神经中观察到L4和L5背根神经节中神经元胞体数量减少67%，证明对抗体07-05（针对pNF表位）具有免疫反应性。综上所述，结果表明，AC抑制远端残端轴突再生减少了轴突切断后神经元核周异常的NF磷酸化
Neurofilaments (NF) are normally poorly phosphorylated in neuronal perikarya and highly phosphorylated in axons. Aberrant NF phosphorylation in the neuronal perikaryon has been demonstrated in a number of human and experimental disorders. In this study, we have asked whether expression of these phosphorylated NF (pNF) epitopes is dependent upon continued axonal regeneration following nerve transection (axotomy). This hypothesis was tested using the neurotoxic chemical acrylamide (AC) which is known to inhibit axonal regeneration following systemic administration. First, we examined whether AC acts at the level of the neuronal perikaryon to inhibit axonal elongation. Systemic, high dose intraperitoneal (IP) AC administration totalling 150 mg/kg (75 mg/kg × 2) did not impair the axotomy-induced reordering of slow axonal transport in the neuronal perikaryon. Next, we studied the ability of AC to directly prevent nerve outgrowth at the growing tips of axons. Subperineurial injection of AC (0.1 M), which in preliminary studies was found not to produce nerve fiber damage, markedly reduced the extent of nerve outgrowth when injected proximal to a nerve crush; this was shown by a reduction in the extent of radiolabeling and number of axonal sprouts in the distal stump seven days following nerve crush. Using this protocol, a 67% decrease in the number of neuronal perikarya in the L4 and L5 dorsal root ganglia demonstrating immunoreactivity to antibody 07-05 (directed against pNF epitopes) was observed in AC-injected compared to contralateral saline-injected crushed nerves. Taken together, the results indicate that inhibition of axonal regeneration in the distal stump by AC reduces aberrant NF phosphorylation in the neuronal perikaryon following axotomy