Toxic neurofilamentous axonopathies and fast anterograde axonal transport. I. The effects of single doses of acrylamide on the rate and capacity of transport.

Acrylamide (ACR) produces a neuropathy in the central and peripheral nervous systems characterized by neurofilament-containing swellings in the distal nerve and eventual dying-back degeneration of axons. The effects of a single exposure to ACR on the rate and quantity of protein transported in the rat sciatic nerve has been measured to determine whether fast axonal transport is compromised by this toxicant. Using the segmental analysis of radioactive label of proteins following 3H-leucine injections into the DRG, ACR (50-100 mg/kg) significantly reduced the rate of fast anterograde transport by 9.3 to 20.8% but, more importantly, reduced the quantity of transported protein by 42.4 to 51.3%. The non-neurotoxic analogue methylene bis-acrylamide did not significantly change either parameter. The reductions in transport were not due to general effects of the toxicant upon protein synthesis. Therefore, fast anterograde transport was significantly affected by a single exposure to ACR in the same magnitude as retrograde transport. Discovery of these dramatic changes was due to differences from previous studies in the time frame of study of transport in relation to toxicant injection and to measurements of the quantity of protein transported rather than only the rate. These changes may be significant in terms of the pathogenesis of distal nerve degeneration.