Early and Dose‐Dependent Decrease of Retrograde Axonal Transport in Acrylamide‐Intoxicated Rats

: The effect on retrograde axonal transport of doses of acrylamide ranging from 50 to 500 mg/kg was studied in sensory nerve of rats. Accumulation of trichloroacetic acid‐phosphotungstic acid‐insoluble label was measured in a collection segment distal to a double ligature placed on the sciatic nerve at intervals 9–15 h and 9–24 h following injection into the dorsal root ganglion of the fifth lumbar root of [35S]methionine and [3H]fucose. After a dose of 100 mg/kg of acrylamide no neurological signs of neuropathy had yet appeared, but retrograde buildup of protein label was significantly reduced for the long interval (2.20 ± 0.49 arbitrary units (AU) (mean ± SD) versus 2.81 ± 0.57 AU in controls, 2p = 0.034). No abnormality of the short interval appeared before a dose of 500 mg/kg was reached. The retrograde transport abnormality was dose‐related (r =−0.85, n = 28 and 2p = 1.2 × 10‐8), as was the degree of neuropathy evaluated by “blind” neurological scoring (r = 0.88, n = 14 and 2p = 2.8 × 10‐5). After a dose of 500 mg/kg, when the rats were severely disabled with almost total incoordination of the hindlegs, the retrograde accumulation of the long interval was profoundly depressed (1.08 ± 0.28 AU versus 2.81 ± 0.57 AU in controls, 2p = 1.2 × 10‐7). Similar changes were seen in accumulation of glycopro‐tein label. After the rats had recovered for 4–10 weeks neurological signs of neuropathy had disappeared and the transport abnormality had improved. To test the specificity of acrylamide on the retrograde transport defect N‐hydroxymethylacrylamide and methylene‐bisacrylamide, which do not induce neuropathy, were studied. None of these related compounds influenced the transport. These observations imply that in acrylamide intoxication a defect in the amount of material carried by retrograde axonal transport rather than in “turnaround” time or in transport velocity is present, that the transport abnormality precedes the development of neuropathy and that it is related to the degree of the neurological disability. We suggest that the retention of protein in the distal axons is the functional counterpart of the well‐known accumulation of vesicular organelles in the pre‐terminals.