TOXIC NEUROFILAMENTOUS AXONOPATHIES AND FAST AXONAL-TRANSPORT .5. REDUCED BIDIRECTIONAL VESICLE TRANSPORT IN CULTURED NEURONS BY ACRYLAMIDEAND GLYCIDAMIDE

Fast axonal transport deficiencies as mechanisms of action of acrylami de in producing axonal degeneration are under evaluation. The current study determines the effects of acrylamide and several analogues on th e number of vesicles moving within the neurite processes of cultured r at embryonic neurons. Acrylamide produced severe, concentration-depend ent (0.25-1.0 mM) and time-dependent (0-60 min) reduction in the quant ity of vesicles translocated in both the anterograde and retrograde di rections. Glycidamide, 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 inhi bition at 60 min, glycidamide was estimated to be 4 times more potent than acrylamide in altering transport. Propionamide, a C-1-C-2 saturat ed nonneurotoxic acrylamide analogue, had no effect on axonal transpor t. While a tendency for methylene bisacrylamide (MbACR) to reduce vesi cle transport was noted, at the concentration used no statistically si gnificant 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 acryla mide and its analogues.