Neurofilament antigens in acrylamide neuropathy.
After repeated exposure, acrylamide (AC) produces degeneration of distal axons. Because neurons whose axons have been injured (e.g. by axotomy) show alterations in their structural and chemical properties, the present study was designed to differentiate the direct effects of AC intoxication from neuronal responses secondary to axonal injury caused by AC. Rats were given AC as either a single high dose (75 mg/kg), or as daily intraperitoneal injections (30 mg/kg, six days per week for four weeks). Dorsal root ganglia of the fifth lumbar level, L5, were examined using a variety of monoclonal antibodies directed against nonphosphorylated (2-135) and phosphorylated (03-44, 06-17, 07-05) epitopes of 145 and 200 kilodalton neurofilament proteins. In control rats, antibody 2-135 stained axons and neuronal cell bodies; antibodies against phosphorylated epitopes of neurofilaments stained only axons distal to the glomerulus. Following chronic AC intoxication, all three antibodies directed against phosphorylated epitopes of neurofilaments (particularly 07-05) demonstrated intense immunoreactivity in 20-30% of neuronal cell bodies. In addition, the glomerular region of these axons was stained. Electron microscopy revealed many chromatolytic cells containing few neurofilaments. In contrast, a single high dose of AC produced no abnormal staining of neuronal cell bodies at a time when slow axonal transport was impaired. Our findings are compared to those observed following axotomy and to those occurring in aluminum-intoxicated rabbits, two experimental disorders in which altered distributions of phosphorylated filaments have been documented.
Gold
B G
BG
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland.
Price
D L
DL
Griffin
J W
JW
Rosenfeld
J
J
Hoffman
P N
PN
Sternberger
N H
NH
Sternberger
L A
LA
D000178:Acrylamides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000941:Antigens; D001369:Axons / Q000473:pathology; D002908:Chronic Disease; D003599:Cytoskeleton / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology; D007382:Intermediate Filaments / Q000276:immunology*; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains
D000178:Acrylamides; D000941:Antigens