ACRYLAMIDE-INDUCED DISTAL AXON DEGENERATION - A PROPOSED MECHANISM OFACTION

Exposure to acrylamide (ACR) monomer produces distal swelling and subs equent degeneration in central and peripheral myelinated axons of huma ns and laboratory animals. The molecular and cellular events leading t o this type of axonopathy are currently unknown. Herein we describe a new mechanism of ACR axonopathy that represents a synthesis of recent research findings and prior hypotheses. According to this model, ion r egulation in distal paranodal axon regions is compromised by diminishe d axolemmal Na/K-ATPase activity. It is suggested that decreased NA/K- ATPase activity is a consequence of aberrant cell body processing and/ or deficient axonal transport. Reduced Na pump activity promotes membr ane depolarization in conjunction with axoplasmic accumulation of Na a nd loss of K. Thermodynamically, this favors reverse operation of the Na/Ca-exchanger which permits axonal Ca entry in exchange for Na. The influx of Ca eventually overwhelms buffering mechanisms and leads to d istal axon degeneration. Distal axons are predisposed to regulatory fa ilure of this type due to a dependency on cell body output and the uni que differential distribution of enzymes, ion channels and exchangers among nodal and internodal regions. This heuristic model might account for axon degeneration occurring as a result of exposure to other chem ical neurotoxicants and following axotomy and other forms of mechanica l injury. (C) 1994 Intox Press, Inc.