Acrylamide neuropathy and changes in the axonal transport and muscular content of the molecular forms of acetylcholinesterase

Abstract

Acetylcholinesterase (AChE) is present in nervous and muscular tissues of normal chickens in four main molecular forms (G1, G2, G4, and A12), distinguishable by sedimentation analysis. In the sciatic nerve of acrylamide-poisoned chickens, the anterograde axonal transport of A12 AChE was reduced by 60%, and that of G4 by 21%, compared to control values whereas the slow axoplasmic transport of G1 and G2 was unaffected. Regarding the leg muscles, only the tibialis anterior revealed dramatic alterations in the distribution of it AChE forms coinciding with a large reduction in the number of nerve endings. In acrylamide poisoning, the AChE molecular forms were considered as very sensitive markers of both axonal transport phases and of the innervation state. Our results support the hypothesis that a defect in the fast axonal transport of proteins might be involved in the degeneration process of the disease.

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

“…Further experimental support for a transport abnormality in acrylamide neuropathy comes from two studies of intoxicated chickens. The one report examined the various molecular forms of acetylcholinesterase and described that an increasing portion of the high-molecular-weight forms (20s) became stationary (Couraud et al, 1982). In the other report, an abnormal retention of fast-transported proteins within the pathological accumulations of smooth endoplasmic reticulum of cranial nerve was demonstrated in a radioautographic study (Chretien et al, 1981).…”

Neurobiology of Acetylcholine

“…Both these compounds cause damage in the central and peripheral nervous systems, motor and sensory systems both being affected (Spencer and Schaumburg, 1977). Couraud et al (1982) have studied the effects of acrylamide exposure on AChE in nerve and muscle of chickens. They found changes in AChE and its molecular forms in the tibialis anterior similar to those seen after denervation.…”

“…AChE, therefore, does not appear a sensitive indicator of neural disturbances. This does not rule out, however, that axonal transport of AChE may prove to be a better marker of axonal damage, as evidenced in the chicken byCouraud et al (1982).In conclusion, muscle AChE is a good marker of the hexacarbon induced neuropathy, exhibiting significant alterations well in advance of any clinical signs of gait disturbances. Analysis of the molecular forms revealed that non-end plate forms of AChE are far more sensitive to early neural disturbances by 2,5-hexanedione exposure than the endplate specific form, A12.…”

Neurotoxic acrylamide and neurotrophic melanocortin peptides–can contrasting actions provide clues about modes of action?

“…An effect of acrylamide on the loading system would result in both a decrease in the amount of label transported and distal accumulation (Figure 2). As most of the rapidly transported proteins participate in the stationary/mobile exchange occurring in transit along the axon (Mfinoz-Martinez, 1982) the scheme shown in Figure 2 would also explain the shift from the transported to the stationary phases reported for glycoproteins (Harry et al, 1989) and some forms of the enzyme acetyl- cholinesterase (Couraud et at., 1982). It is, for obvious technical reasons, not possible to determine whether the same rapid effect of acrylamide occurs in the slow transport system.…”