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

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 pero xidase (HRP) in dissociated dorsal root ganglia (DRG) neurons and neurons o f explant cultures of DRG. Different exposure periods (1 and 6 hours as wel l as 6 and 10 days) to aluminium were analysed quantitatively. This analysi s revealed an impaired anterograde transport of HRP already after a short a luminium intoxication period of only 1 hour in DRG cells in vitro, an effec t that increased with a prolonged aluminium exposure for up to 10 days. Hen ce, functional alterations of the anterograde transport caused by aluminium could be detected even after short exposure periods. Furthermore, the effe cts of aluminium on anterograde transport mechanisms were reversible 8 days after removal of aluminium. To determine how aluminium affects the cytoske leton, we performed immunohistochemistry and electron microscopy on culture d DRG neurons. Distinct morphological alterations of the cytoskeleton, espe cially the accumulation of phosphorylated neurofilaments, appeared after 6 days of aluminium exposure. Our results suggest that neurofilaments are ind ispensable to the functional integrity of the cytoskeleton and its ability to mediate microtubule-based axonal transport processes.