Acrylamide-induced alterations in axonal transport. Biochemical and autoradiographic studies.
Alterations in the axonal transport of proteins, glycoproteins, and gangliosides in sensory neurons of the sciatic nerve were examined in adult male rats exposed to acrylamide (40 mg ip/kg body wt/d for nine consecutive days). Twenty-four hours after the last dose, the L5 dorsal root ganglion (DRG) was injected with either [35S]methionine to label proteins or [3H]glucosamine to label glycoproteins and gangliosides. The downflow patterns of radioactivity for [35S]methionine-labeled proteins and [3H]glucosamine-labeled gangliosides were unaltered by acrylamide treatment. In contrast, the outflow pattern of labeled glycoproteins displayed a severely attenuated crest with no alteration in velocity, suggesting a preferential transfer with the unlabeled stationary components in the axolemma. Retrograde accumulation of transported glycoproteins and gangliosides was unaltered for at least 6 h; however, by 24 h, there was a 75% decrease in the amount of accumulated material. The accumulation of [35S]methionine-labeled proteins was not altered. Autoradiographic analysis revealed an acrylamide-induced paucity of transported radiolabeled glycoproteins selectively in myelinated axons with no effect on "nonmyelinated" axons. The pattern of transported proteins was similar in both control and acrylamide-exposed animals. These results suggest a preferential inhibition of glycosylation or axonal transport of glycoproteins in neurons bearing myelinated axons. More importantly, it suggests that interpretations of axonal transport data must be made with the consideration of alterations in selective nerve fibers and not with the tacit assumption that all fibers in the nerve population are equally affected.
D020106:Acrylamide; D000178:Acrylamides / Q000633:toxicity*; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001370:Axonal Transport / Q000187:drug effects*; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D005727:Ganglia, Spinal / Q000502:physiology*; D005732:Gangliosides / Q000096:biosynthesis / Q000378:metabolism; D005944:Glucosamine / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000378:metabolism; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D012584:Sciatic Nerve / Q000502:physiology*; D013462:Sulfur Radioisotopes; D014316:Tritium
D000178:Acrylamides; D005732:Gangliosides; D006023:Glycoproteins; D009498:Neurotoxins; D013462:Sulfur Radioisotopes; D014316:Tritium; D020106:Acrylamide; D008715:Methionine; D005944:Glucosamine