Regulation of aberrant neurofilament phosphorylation in neuronal perikarya. I. Production following colchicine application to the sciatic nerve.
Regulation of aberrant neurofilament phosphorylation in neuronal perikarya. I. Production following colchicine application to the sciatic nerve.
复制标题
神经元周核异常神经丝磷酸化的调节。
DOI：
10.1097/00005072-199109000-00007
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发表时间：
1991
影响因子：
3.2
通讯作者：
Austin,DR
中科院分区：
文献类型：
--
作者：
Gold,BG;Austin,DR
神经丝蛋白三联体蛋白在神经元核膜中的磷酸化程度通常很低，一旦神经丝进入轴突，这两种高分子量的多肽就会被广泛的磷酸化。在不同的人类和实验条件下，使用单抗已经发现了在神经元核周异常表达的磷酸化的核因子(PNF)表位。在目前的研究中，我们询问了在阻断快速轴突运输后，在L4和L5背根节(DRG)的感觉神经元中是否有pNF表位的表达，这是一个产生少量(1%)变性纤维的模型。秋水仙碱(5 Mm)短暂(45分钟)应用于大腿中部的坐骨神经，两次(每周一次)，动物在第一次应用秋水仙碱后两周进行研究；对侧神经要么用生理盐水处理，要么被挤压。抗07-05抗体(针对两个大分子神经营养因子多肽上的pNF表位)在秋水仙碱处理神经和损伤神经中分别有30.4%和45.1%的DRG神经元呈中到强免疫反应，仅有极少数胞体在对侧生理盐水处理的神经中呈免疫染色。单次使用秋水仙碱后第2天和第5天，抗体07-05未观察到免疫反应。在另一项研究中，秋水仙碱或生理盐水(如上所述)在神经挤压的近端1-2厘米处应用。应用秋水仙碱不影响DRG神经元表达pNF表位的程度；在生理盐水和秋水仙碱处理的损伤神经中，分别有44.7%和43.8%的DRG神经元表达抗体07-05。结果表明，神经-靶点接触的结构中断并不是诱导神经元核周异常核因子磷酸化的必要条件。有人认为，失去逆行运输的“营养”信号(S)触发了这一反应。
Neurofilament (NF) triplet proteins are normally poorly phosphorylated in neuronal perikarya, the two high molecular weight polypeptides becoming extensively phosphorylated once the NF enters the axon. Abnormal expression of phosphorylated NF (pNF) epitopes in neuronal perikarya has been revealed using monoclonal antibodies in a variety of human and experimental conditions. In the present study, we asked whether pNF epitopes are expressed in sensory neurons in the L4 and L5 dorsal root ganglia (DRG) following blockade of fast axonal transport in a model producing few (< 1%) degenerating fibers. Colchicine (5 mM) was briefly (45 minutes) applied to the sciatic nerve at mid-thigh twice (once weekly) and the animals studied two weeks following the first colchicine application; contralateral nerves were either treated with saline or crushed. Modest to intense immunoreactivity was found with antibody 07-05 (directed against pNF epitopes on the two high molecular weight NF polypeptides) in 30.4% and 45.1% of DRG neurons from colchicine-treated and crushed nerves, respectively; only a rare cell body demonstrated immunostaining from the contralateral saline-treated nerves. Immunoreactivity was not observed with antibody 07-05 at two and five days following single colchicine application. In a separate study, colchicine or saline was applied (as above) 1–2 cm proximal to a nerve crush. Colchicine application did not influence the extent of DRG neurons expressing pNF epitopes; immunostaining with antibody 07-05 was present in 44.7% and 43.8% of DRG neurons from saline-treated and colchicine-treated crushed nerves, respectively. The results indicate that structural interruption of nerve-target contact is not necessary to induce aberrant NF phosphorylation in neuronal perikarya. It is suggested that loss of a retrogradely transported “trophic” signal(s) triggers this response.