Toxic neurofilamentous axonopathies and fast axonal transport. v. reduced bidirectional vesicle transport in cultured neurons by acrylamide and glycidamide

Fast axonal transport deficiencies as mechanisms of action of aoylamide in producing axonal degeneration are under evaluation. The current study determines the effects of acry- lamide and several analogues on the number of vesicles moving within the neurite processes of cultured rat embryonic neurons. Acrylamide produced severe, concentration- dependent (0.25-1.0 mM) and time-dependent (0-60 min) reduction in the quantity of vesicles translocated in both the anterograde and retrograde directions. Clycidamide, a potential neurotoxic metabolite of acrylamide, produced a time-dependent but not a concentration-dependent (in the 0.25-1.0 mM range) reduction in bidirectional transport. Based on inhibition at 60 min, glycidamide was estimated to be 4 times more potent than acrylamide in altering transport. Propionamide, a C₁,-C₂saturated nonneurotoxic acrylamide analogue, had no effect on axonal transport. While a tendency for methylene bisacrylamide (MbACR) to reduce vesicle transport was noted, at the concentration used no statistically significant differences from control were observed. The data support the correlation between toxicant-induced fast anterograde and retrograde axonal transport reductions and axonal degeneration produced by acrylamide and its analogues.