Inhibitory effect of aluminium on the axonal transport of HRP microinjected into dorsal root ganglion neurons in vitro.

Abstract

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.