Theiss C, Meller K
Institut für Anatomie, Abteilung für Cytologie, Ruhr-Universität Bochum, Universitätsstrasse 150, D-44780 Bochum, Germany.
J Neurocytol. 2001 Jan;30(1):59-71. doi: 10.1023/a:1011969408520.
In the present study the function of axonal transport in individual neurons under aluminium intoxication was investigated experimentally in comparison with controls. We used the technique of microinjection of horseradish peroxidase (HRP) in dissociated dorsal root ganglia (DRG) neurons and neurons of explant cultures of DRG. Different exposure periods (1 and 6 hours as well as 6 and 10 days) to aluminium were analysed quantitatively. This analysis revealed an impaired anterograde transport of HRP already after a short aluminium intoxication period of only 1 hour in DRG cells in vitro, an effect that increased with a prolonged aluminium exposure for up to 10 days. Hence, functional alterations of the anterograde transport caused by aluminium could be detected even after short exposure periods. Furthermore, the effects of aluminium on anterograde transport mechanisms were reversible 8 days after removal of aluminium. To determine how aluminium affects the cytoskeleton, we performed immunohistochemistry and electron microscopy on cultured DRG neurons. Distinct morphological alterations of the cytoskeleton, especially the accumulation of phosphorylated neurofilaments, appeared after 6 days of aluminium exposure. Our results suggest that neurofilaments are indispensable to the functional integrity of the cytoskeleton and its ability to mediate microtubule-based axonal transport processes.
在本研究中，通过与对照组比较，对铝中毒情况下单个神经元轴突运输的功能进行了实验研究。我们采用向离体背根神经节（DRG）神经元及DRG外植体培养神经元中显微注射辣根过氧化物酶（HRP）的技术。分析了不同铝暴露时间（1小时和6小时以及6天和10天）的情况。该分析显示，在体外DRG细胞中，仅1小时的短时间铝中毒后，HRP的顺向运输就已受损，且随着铝暴露时间延长至10天，这种效应会增强。因此，即使在短暴露时间后，也能检测到铝对顺向运输的功能改变。此外，去除铝8天后，铝对顺向运输机制的影响是可逆的。为确定铝如何影响细胞骨架，我们对培养的DRG神经元进行了免疫组织化学和电子显微镜检查。铝暴露6天后，细胞骨架出现明显的形态学改变，尤其是磷酸化神经丝的积累。我们的结果表明，神经丝对于细胞骨架的功能完整性及其介导基于微管的轴突运输过程的能力不可或缺。
