Anterograde Axonal Transport in Rats During Intoxication with Acrylamide

Abstract

Anterograde axonal transport was examined in sensory nerves of rats intoxicated with a low dose (group I) or a high dose (group II) of acrylamide. After injection of either [35S]methionine and [3H]fucose or [3H]proline into the dorsal root ganglia of the 5th lumbar roots, distribution of protein label was measured in 3‐mm segments of the sciatic nerve at intervals of 2 h, 4 h, 10 days, and 26 days. No difference in ganglion incorporation was present at 4 h, and the fast transport velocity of methionine label also remained normal [14.7 ± 1.3 mm/h (mean ± SD) in controls versus 14.6 ± 0.3 mm/h and 15.4 ± 1.2 mm/h in acrylamide group I and II, respectively]. Neither was there any decrease in transport velocity of proline label of slow component b (4.18 ± 0.29 mm/day in controls versus 4.29 ± 0.17 mm/d and 4.22 ± 0.29 mm/day in acrylamide group I and II, respectively). In slow component a, however, a significant reduction in the fractional amount of proline label was found (20.8 ± 4.0% in controls versus 17.6 ± 14.9% and 9.7 ± 5.9% in acrylamide group I and II, respectively). Again no decrease in transport velocity was observed (1.03 ± 0.02 mm/day in controls versus 1.06 ± 0.08 mm/day and 1.07 ± 0.03 mm/day in acrylamide group I and II, respectively), and closer inspection of the activity along the nerve did not reveal any alteration in skewness or ‘peakedness’ of the distribution curve. The reduction in amount of protein carried in the slow axonal transport component in rats with severe acrylamide neuropathy (group II) could be associated with fibre breakdown at a late stage of the neuropathic process. The most important consequence of the study is, however, that in contrast to previous suggestions, during acrylamide intoxication no changes are present in protein incorporation or in anterograde axonal transport which can explain the initial pathological or functional abnormalities of the distal axons.

Continuous Delivery of Neurotrophin 3 by Gene Therapy Has a Neuroprotective Effect in Experimental Models of Diabetic and Acrylamide Neuropathies

“…Experimental di- abetic and high-level acrylamide-induced neuropathies also have several characteristics in common. Indeed, abnormalities of retrograde and anterograde axonal transport are considered to be an important pathogenic mechanism of both experimental acrylamide (Sidenius and Jakobsen, 1983;Miller and Spencer, 1984) and diabetic neuropathy (Jakobsen and Sidenius, 1980;Jakobsen et al, 1981). Neurotransmitter modifications in rat enteric nerve, common to both acrylamide and diabetic experimental neuropathies, have suggested a common pathogenic mechanism (Belai and Burnstock, 1996).…”

Anterograde Fast Component of Axonal Transport During Insulin-Induced Hypoglycemia in Nondiabetic and Diabetic Rats

“…The aFC was investigated as described earlier (8,9). Labeled methionine (L-[ 35 S]methionine, 37.4-55.0 TBq/mmol, Amersham, Arlington Heights, IL) was used as a marker for protein, and tritiated fucose (i_-[5,6-3 H]fucose, 1.85-2.48 TBq/mmol, Amersham) was used to mark glycoprotein.…”

“…1) was described by the following parameters: activity in the ganglion (4 h after injection), activity in aFC (4 h), the fraction of activity in aFC relative to the activity in the ganglion, the height of the plateau, the span of the wave front, the maximal transport velocity, and the lag time (8,9). The activity was counted by liquid scintillation in 4 ml Lipoluma (Lumac) and expressed in disintegrations per minute.…”

Single Doses of Acrylamide Reduce Retrograde Transport Velocity

“…ylene-bis-acrylamide which produce generalized systemic toxicity (severe weight loss and death) upon repeated administration is of unknown significance. Administration of acrylamide, however, in doses equal to 50 mg/kg (0.65 mmol/kg) or less re-T'he specific role that altered retrograde transport may Serve in the etiology of acrylamide-induced ax-Onopathy has yet to be Jakobsen and Sidenius (1983) suggested that altered retrograde transport, in the presence of essentially normal fast anterograde transport (Bradley and williams, 1973;Sumner et al, 1976;Griffin and Price, 1976;Sidenius and Jakobsen, 1983), may be responsible for the accumulation of multivesicular bodies and tubuiovesicular structures in distal portions of axons from acrylamide-treated animals Griffin et al, 1977). The profound alterations in retrograde transport reported herein are (Cragg, 1970;Kristensson and Sjostrand, 1972;Pilar and Landmesser, 1972;Grafstein, 1975;Bisby and Bulgar, 1977;Singer et al, 1982).…”

“…These axonal swellings often contain paranodal accuriiulations of neurofilaments and multilamellar bodies (Prineas, 1969;Hopkins, 1970;Spencer and Schaumburg, 1977), findings suggestive of alterations in axonal transport (Prineas, 1969;Spencer and Schaumburg, 1974). Studies of fast and slow anterograde axonal transport in animals treated with acrylamide have revealed no marked changes (Bradley and Williams, 1973;Sumner et al, 1976;Griffin and Price, 1976;Sidenius and Jakobsen, 1983). Recent studies have demonstrated altered retrograde transport of horseradish peroxidase (Kemplay and Cavanagh, 1983) and of materials which have "turned around" following fast anterograde axonal transport in animals repeatedly dosed With acrylamide that demonstrate signs of neuropathy (Sahenk and Mendell, 1981;Jakobsen and Sidenius, 1983).…”