Regulation of aberrant neurofilament phosphorylation in neuronal perikarya. III. Alterations following single and continuous beta, beta'-iminodipropionitrile administrations.
Regulation of aberrant neurofilament phosphorylation in neuronal perikarya. III. Alterations following single and continuous beta, beta'-iminodipropionitrile administrations.
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神经元周核异常神经丝磷酸化的调节。
DOI：
10.1016/0006-8993(91)91528-9
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发表时间：
1991
期刊：
影响因子：
2.9
通讯作者：
Austin,DR
中科院分区：
文献类型：
--
作者：
Gold,BG;Austin,DR
β,β'-亚氨基二丙腈 (IDPN) 给药会在大有髓鞘感觉和运动纤维的第一近端节间产生巨大的充满神经丝的轴突肿胀，而不会伴随任何轴突变性。在本研究中，我们询问近端巨大轴突肿胀是否足以引起神经元核周异常神经丝（NF）磷酸化。给大鼠单次腹膜内 (i.p.) 注射 IDPN (2 g/kg)，然后在饮用水（持续 IDPN 暴露）或自来水（单次 IDPN 暴露）中注射 IDPN (0.1%)，持续两天至 7 周。在 L4 和 L5 背根神经节 (DRG) 神经元中观察到磷酸化 NF (pNF) 表位（使用单克隆抗体 6-17 和 7-05）的免疫反应性开始于 1 至 5 天，对应于近端巨大轴突肿胀的发展。 DRG 神经元的定量显示，一周时对 pNF 表位产生免疫反应的细胞体数量达到最大 (46-51%)。在连续暴露于 IDPN 的动物中，免疫染色的 DRG 细胞数量得以维持，但在单次注射 IDPN 的大鼠中，在第 3 周和第 5 周分别显着下降（P<0.001）至 26 ± 0.80% 和 6 ± 0.04%。腹侧和背根纤维在轴突肿胀远端发生轴突萎缩，对 pNF 表位表现出强烈的免疫反应性，并且对抗体 2-135（针对非磷酸化 NF 表位）的免疫染色显着减少或完全缺乏；用碱性磷酸酶预处理逆转了这种染色模式。在另一项研究中，神经挤压后 4 周后，在 DRG 的萎缩运动纤维中也观察到了类似的碱性磷酸酶敏感的抗体 2-135 染色缺失。这表明，IDPN 处理的大鼠 DRG 神经元细胞体中异常的 NF 磷酸化继发于由于巨大轴突肿胀的存在而逆向传输至神经元的“营养”信号的改变。此外，萎缩轴突中的 pNF 可能对应于轴浆中静止或缓慢移动的 NF。
β,ß′-Iminodipropionitrile (IDPN) administration produces giant neurofilament-filled axonal swellings in the first proximal internodes of large myelinated sensory and motor fibers without any accompanying axonal degeneration. In the present study, we asked whether proximal giant axonal swellings are sufficient to elicit aberrant neurofilament (NF) phosphorylation in neuronal perikarya. Rats were given a single intraperitoneal (i.p.) injection of IDPN (2 g/kg) followed by IDPN (0.1%) in the drinking water (continuous IDPN exposure) or tap water (single IDPN exposure) for two days to 7 weeks. Immunoreactivity to phosphorylated NF (pNF) epitopes (using monoclonal antibodies 6–17 and 7–05) was observed in L4and L5dorsal root ganglia (DRG) neurons beginning between one and 5 days, corresponding to the development of proximal giant axonal swellings. Quantitation of DRG neurons demonstrated maximal numbers of immunoreactive cell bodies to pNF epitopes (46–51%) by one week. The number of immunostained DRG cells was maintained in animals given continuous IDPN exposure, but declined significantly (P< 0.001) in rats given a single injection of IDPN to 26 ± 0.80% and 6 ± 0.04% at 3 and 5 weeks, respectively. Ventral and dorsal root fibers, which undergo axonal atrophy distal to axonal swellings, showed intense immunoreactivity to pNF epitopes and a marked reduction or a complete lack of immunostaining to antibody 2–135 (directed against non-phosphorylated NF epitopes); pretreatment with alkaline phosphatase reversed this staining pattern. In a separate study, a similar alkaline phosphatase-sensitive lack of staining to antibody 2–135 was also observed in atrophic motor fibers in the DRG 4 weeks following nerve crush. It is suggested that aberrant NF phosphorylation in DRG neuronal cell bodies from IDPN-treated rats arises secondarily to an alteration in a retrogradely transported ‘trophic’ signal(s) to the neuron due to the presence of giant axonal swellings. Furthermore, pNFs in atrophic axons may correspond to stationary or slowly moving NFs in the axoplasm.