The Mechanisms of Acrylamide Axonopathy

Abstract

Degeneration of the distal axons of long and large-diameter peripheral nerve fibers is perhaps the most common of all toxic peripheral nerve disorders. Degeneration commonly spreads centrally along affected nerve tracts in a dying-back fashion (1). Axonal disorders of this type are grouped under the term central-peripheral distal axonopathy to emphasize the contemporaneous onset of distal retrograde axonal degeneration in long nerve-fiber tracts in both the central nervous system (CNS) and the peripheral nervous system (PNS) (2). Axonopathy refers exclusively to the primary degeneration of axons, although associated changes may occur in corresponding neuronal perikarya. Schwann cells and oligodendrocytes enveloping affected axons in the PNS and CNS, respectively, commonly undergo secondary changes, induding mitosis and loss of myelin maintenance, while fibroblasts and astrocytes become involved later in the degenerative process. Distal axonopathy can result from a single or, more commonly, repeated exposure to a variety of chemically unrelated agents, or it can occur with apparent spontaneity in a number of abnormal nutritional or metabolic states (3). Although the biochemical mechanisms underlying axonal degeneration are unknown, some progress has been made in recent years in understanding the biochemical events that precede and accompany axon degeneration in certain toxic neuropathies, notably those associated with repeated exposure to acryla­ mide or aliphatic ,),-diketones. Multidisciplinary investigation of these neurop­ athies in laboratory animals and organotypic tissue cultures has revealed several previously unknown basic mechanisms that may be involved in the maintenance of the axon and the initiation and regulation of the degenerative