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.