Somatofugal axonal atrophy precedes development of axonal degeneration in acrylamide neuropathy

Abstract

Somatofugal axonal atrophy is part of the neuronal perikaryal response to axonal injury (axon reaction). Chronic administration of acrylamide (AC) produces proximal atrophy in virtually all sensory fibers in lumbar dorsal root ganglion (DRG) despite the presence of many intact axons in the distal portion of the sciatic nerve. This suggests that the development of axonal atrophy in AC-intoxicated animals is not solely due to a toxic chemical-induced axonal degeneration (axotomy). In this study, we asked whether axonal atrophy arises before onset of axonal degeneration. Rats were given a single intraperitoneal (i.p.) high dose of AC (75 mg/kg), which blocks retrograde axonal transport, followed by daily intraperitoneal injections (30 mg/kg, for 4 days). At 5 days, sensory fibers in the L4 and L5 DRG appeared smaller in caliber and less circular in shape compared to fibers from age-matched normal animals. Axonal diameters of sensory fibers in the L5 dorsal root were significantly (p less than 0.05) reduced at distances up to 2 mm from the DRG. Quantitative electron microscopy demonstrated that the reduction in caliber was due to a decreased neurofilament (NF) content. Axonal degeneration was not present in the distal portion of both centrally (dorsal root) and peripherally (sciatic nerve) projecting sensory fibers at this time, although primary afferent terminals in muscles of the hindfeet were packed with NFs. The somatofugal progression of the atrophy was evident following more prolonged exposures (10-28 days). It is suggested that AC produces somatofugal axonal atrophy by inhibiting the delivery of a retrogradely transported target-derived "trophic" signal to the neuronal perikaryon.

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

“…Indeed, acrylamide neuropathy is sensitive before the onset of motor involvement and impairs the autonomic nervous system (Schaumburg et al, 1974;Ralevic et al, 1991). Administration of high doses of acrylamide induces somatofugal axonal atrophy, which precedes the development of axonal degeneration (Gold et al, 1992). Therefore, the experimental neuropathy does not progress as a distal axonopathy, which is a frequent feature of diabetic neuropathy (Said et al, 1983).…”

Glial Cells in Neurotoxicity Development

“…diabetic neuropathy) and exposure to certain neurotoxic chemicals (e.g. acrylamide, hexanedione, and carbon disulfide) are associated with axonal atrophy and reduced peripheral nerve conduction velocity (110)(111)(112)(113). Based on the above, it is possible that reduced fiber caliber in these conditions is secondary to an uncoupled Schwann cell-axon relationship, demyelination, or both.…”

Acrylamide Alters Cytoskeletal Protein Level in Rat Sciatic Nerves

“…As ACR intoxication continued, axonal regions below these swellings degenerated [9]. However, other studies showed that chronic intoxication with ACR leads to axonal atrophy, which precedes development of axonal degeneration [10,11]. Historically, this type of nerve damage has been classified as a centralperipheral distal axonopathy and is presumably to be responsible for the associated neurological defects.…”