Acrylamide‐Induced Increases in Deposition of Axonally Transported Glycoproteins in Rat Sciatic Nerve

Abstract

The axonal transport of proteins, glycoproteins, and gangliosides in sensory neurons of the sciatic nerve was examined in adult rats exposed to acrylamide via intraperitoneal injection (40 mg/kg of body weight/day for nine consecutive days). The L5 dorsal root ganglion was injected with either [35S]methionine to label proteins or [3H]glucosamine to label, more specifically, glycoproteins and gangliosides. At times ranging from 2 to 6 h later, the sciatic nerve and injected ganglion were excised and radioactivity in consecutive 5-mm segments determined. In both control and acrylamide-treated animals, outflow profiles of [35S]methionine-labeled proteins showed a well defined crest which moved down the nerve at a rate of approximately 340 mm/day. Similar outflow profiles and transport rates were seen for [3H]glucosamine-labeled glycoproteins in control animals. However, in animals treated with acrylamide, the crest of transported labeled glycoprotein was severely attenuated as it moved down the nerve. This finding suggests that in acrylamide-treated animals, axonally transported glycoproteins were preferentially transferred (unloaded or exchanged against unlabeled molecules) from the transport vector to stationary axonal structures. We also examined the clearance of axonally transported glycoproteins distal to a ligature on the nerve. The observed impairment of clearance in acrylamide-treated animals relative to controls is supportive of the above hypothesis. Acrylamide may directly affect the mechanism by which axonally transported material is unloaded from the transport vector. Alternatively, the increased rate of unloading might reflect an acrylamide-induced increase in the demand for axonally transported material.

Acrylamide exposure preferentially impairs axonal transport of glycoproteins in myelinated axons

“…There was a 10-15% decrease in body weights of exposed animals within 5 days of dosing. As previously reported (Harry et al, 1989), light microscopy of semi-thin sections of the sciatic, sural, and tibia1 nerves showed a normal population of myelinated fibers. Electron microscopic analysis of these nerves only rarely showed any degenerative changes in myelinated or unmyelinated axons.…”

“…The acrylamide-induced deficit of labelled glycoprotein in myelinated axons could be accounted for by a block of a processing step at the level of glycosylation, or further along at the level of commitment of glycoproteins to rapid transport down myelinated axons. In our previous study (Harry et al, 1989), we reported that exposure of rats to acrylamide altered the transport kinetics of labelled glycoproteins. This transport abnormality was evidenced by a marked attenuation of the initial crest of transported material.…”

“…The axonal swellings are formed by an accumulation of intermediate filaments and other organelles and are more prominent in the distal regions of the axon (Cavanagh, 1964;Prineas, 1969;Schaumburg et al, 1974; LeQuesne, 1985). Although various investigations have implicated alterations in axonal transport in acrylamideinduced peripheral neuropathy (Sabri and Spencer, 1980;Chretien et al, 1981;Souyri et al, 1981;Griffin et al, 1983;Brimijoin, 1984;Miller and Spencer, 1985;Sayre et al, 1985;Spencer et al, 1985; Ochs, 1987; Moretto and Sabri, 1988), there is no consensus on the exact nature of the transport defect (Sumner et al, 1976;Weir et al, 1978;Sahenk and Mendell, 1981;Sidenius and Jakobsen, 1983;Bisby and Redshaw 1987).We have presented data suggesting that the decreased amount of transported material reaching distal axonal regions in acrylamide neuropathy is related to a greater than normal deposition of transported material during transit ( Harry et al, 1989). Using autoradiographic techniques, we have now examined the sensory fibers in sciatic nerve of acrylamide-exposed rats for alterations in the distribution pattern of rapidly transported labelled material.…”

“…We have presented data suggesting that the decreased amount of transported material reaching distal axonal regions in acrylamide neuropathy is related to a greater than normal deposition of transported material during transit ( Harry et al, 1989). Using autoradiographic techniques, we have now examined the sensory fibers in sciatic nerve of acrylamide-exposed rats for alterations in the distribution pattern of rapidly transported labelled material.…”

Scientific Opinion on acrylamide in food

“…The neurotoxic action of AA was suggested to be due to effects on cells of the central and peripheral nervous system including changes in cellular metabolism (Howland et al, 1980;Brimijoin and Hammond,1985;Medrano and LoPachin, 1989;Exon, 2006), changes in gene transcription and protein synthesis (Cavanagh and Nolan, 1982a,b;Cavanagh, 1982;Cavanagh and Gysbers, 1983;Bisby and Redshaw, 1987;Lin et al, 2000;El-Alfy et al, 2011;Seale et al, 2012), effects on neurotransmitter levels and turn-over (Dixit et al, 1981;Uphouse and Russell, 1981;Aldous et al, 1983;Shi et al, 2012), binding to cellular proteins including damage to microtubular and neurofilamental proteins (Hashimoto and Aldridge, 1970;Tanii and Hashimoto, 1983;Carrington et al, 1991;Reagan et al, 1994;Abou-Donia, 1996, 1997;Lapadula et al, 1989;Xiwen et al, 1992), changes in ion distribution (Lehning et al, 1998;LoPachin and Lehning, 1994), and axonal transport (Chretien et al, 1981;Miller and Spencer, 1984;Gold et al, 1985;Moretto and Sabri, 1988;Logan and McLean, 1988;Harry et al, 1989;Sabri and Spencer, 1990;Martenson et al, 1995;Sickles et al, 1995Sickles et al, ,1996Stone et al, 2001). However, the minimal effects of AA-treatment, by up to a maximally tolerated dose, on: (i) gene expression related to cholinergic, noradrenergic, dopaminergic, GABAergic, or glutamatergic neurotransmitter systems; (ii) neurotransmitter levels related ...…”