Somatofugal axonal atrophy precedes development of axonal degeneration in acrylamide neuropathy.
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.
Gold
B G
BG
Center for Research on Occupational and Environmental Toxicology, Oregon Health Sciences University, Portland 97201.
Griffin
J W
JW
Price
D L
DL
D020106:Acrylamide; D000178:Acrylamides / Q000633:toxicity*; D000818:Animals; D001284:Atrophy; D001369:Axons / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D007382:Intermediate Filaments / Q000187:drug effects; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains
D000178:Acrylamides; D020106:Acrylamide