TY - JOUR
T1 - Toxic neurofilamentous axonopathies and fast axonal transport. v. reduced bidirectional vesicle transport in cultured neurons by acrylamide and glycidamide
AU - Harris, C. H.
AU - Gulati, A. K.
AU - Friedman, M. A.
AU - Sickles, D. W.
N1 - Funding Information:
Received 9 April 1993; accepted 8 December 1993. Funding for this study was provided by American Cyanamid Company, Wayne, N.J. Address correspondenceto D. W. Sickles, Department of Cellular Biology and Anatomy, College of Georgia, Augusta, CA 30912-2000, USA.
PY - 1994/7
Y1 - 1994/7
N2 - 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.
AB - 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.
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U2 - 10.1080/15287399409531884
DO - 10.1080/15287399409531884
M3 - Article
C2 - 7517455
AN - SCOPUS:0028175589
SN - 0098-4108
VL - 42
SP - 343
EP - 356
JO - Journal of Toxicology and Environmental Health
JF - Journal of Toxicology and Environmental Health
IS - 3
ER -