Single Doses of Acrylamide Reduce Retrograde Transport Velocity

Abstract

Single doses of acrylamide (0-1.3 mmol/kg) produced a dose-dependent decrease in the transport of 125I-tetanus toxin to the perikarya of sensory neurons in dorsal root ganglia and motor neurons in ventral spinal cord. Acrylamide was a more potent inhibitor of retrograde transport in sensory axons than in motor axons. Substantially greater doses of N,N'-methylene-bis-acrylamide, a reportedly non-neurotoxic analog of acrylamide, were required to alter the axonal transport of 125I-tetanus toxin. Velocity of retrograde transport was assessed by determining the position of the leading edge of transported 125I-tetanus toxin at times following single doses of acrylamide. Acrylamide reduced the velocity of 125I-tetanus toxin transport in a dose-dependent manner by up to 75%. No change in neuronal uptake of 125I-tetanus toxin was detected. It is concluded that single doses of acrylamide produce profound alterations in retrograde transport which precede the appearance of structural changes in affected nerve fibers.

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 ...…”

Number and volume of rat dorsal root ganglion cells in acrylamide intoxication

“…Similar changes are also seen in the neurofilamentous neuropathies caused by 2.5-hexanedione, carbondisulfide and IDPN. In studies of axonal transport it has been shown that the retrograde fast transport of tetanus toxin and exogenous NGF is decreased early in acrylamide intoxication Miller et al, 1983;Miller & Spencer, 1984). The retrograde fast transport is believed to carry trophic factors, e.g.…”

Somatofugal axonal atrophy precedes development of axonal degeneration in acrylamide neuropathy

“…Moreover, some of the perikaryal changes which precede frank axonal degeneration may arise secondary to an alteration in "trophic" regulation of the cell body, perhaps due to a defect in retrograde axonal transport (Jakobsen and Sidenius 1983;Miller et ai. 1983;Miller and Spencer 1984). In this case, neuronal perikarya from AC-intoxicated animals would be expected to demonstrate alterations similar to those produced by axotomy (Gold et al 1985(Gold et al , 1988.…”